Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(C(CCC)CCCC(NCC1C=CC=CC=1)CO)CC.C1OC1.O[CH2:26][CH2:27][N:28]([CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[CH:29]([CH2:32][CH2:33][CH2:34][CH:35]([CH2:39][CH2:40][CH3:41])[CH2:36][CH2:37][CH3:38])[CH2:30][OH:31].S(=O)(=O)(O)O.[OH-].[Na+]>C(O)C>[CH2:42]([N:28]1[CH2:27][CH2:26][O:31][CH2:30][CH:29]1[CH2:32][CH2:33][CH2:34][CH:35]([CH2:39][CH2:40][CH3:41])[CH2:36][CH2:37][CH3:38])[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1
Reactant: CCCC(CCC)CCCC(CO)N(CCO)Cc1ccccc1
Agent: CCCC(CCC)CCCC(CO)NCc1ccccc1
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: CCO
Solvent: C1CO1
Product: CCCC(CCC)CCCC1COCCN1Cc1ccccc1
Reaction time: 3 h
Yield: 93 %

Procedure:
46.6 grams (0.16 mole) of 6-propyl-2-benzylamino-1-nonanol and 11 grams (0.20 moles) of ethylene oxide in 200 ml. 96% ethanol were kept at 100° C. in an autoclave with careful stirring for three hours. The reaction mixture was evaporated. 57 grams (100%) of GLC-unitary substance were obtained, viz. N-(2-hydroxyethyl)-6-propyl-2-benzylamino-1-nonanol. Said 57 grams were dissolved in 450 ml. of 70% (w/w) sulfuric acid and kept in a glass autoclave at 140°-150° C. for 15 hours. The reaction mixture was admixed with an excess of 40% aqueous NaOH and extracted with diethyl ether. The ether extract was dried over sodium sulphate and evaporated. Distillation gave 49.7 grams (93%) N-benzyl-3-(4-propyl-heptyl)morpholine, boiling point 163°-165° C./0.01 mm Hg. This substance (49.7 grams) and 3 grams of 10% (w/w) Pd-C in 500 ml. 96 % ethanol were hydrogenated in a steel autoclave at 100° C. and 100 atmospheres hydrogen pressure for 12 hours. Conventional processing gave 34.2 grams (96%) of 3-(4-propyl-heptyl)morpholine, boiling point 76°-78° C./0.01 mm Hg. The base obtained was dissolved in ether and the hydrochloride precipitated with hydrochloric acid in ethanol. Recrystallization gave crystals having a melting point of 118°-119° C.
Reaction SMILES: [CH3:1][CH:2]1[CH2:7][CH2:6][CH2:5][CH2:4][CH:3]1[CH2:8][OH:9].C(=O)([O-])[O-].[Cs+].[Cs+].[Cl:16][C:17]1[C:18](F)=[CH:19][C:20]([F:30])=[C:21]([CH:29]=1)[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23].Cl>CS(C)=O>[Cl:16][C:17]1[C:18]([O:9][CH2:8][CH:3]2[CH2:4][CH2:5][CH2:6][CH2:7][CH:2]2[CH3:1])=[CH:19][C:20]([F:30])=[C:21]([CH:29]=1)[C:22]([O:24][C:25]([CH3:26])([CH3:27])[CH3:28])=[O:23]
Reactant: CC1CCCCC1CO
Reactant: CC(C)(C)OC(=O)c1cc(Cl)c(F)cc1F
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CS(C)=O
Product: CC1CCCCC1COc1cc(F)c(C(=O)OC(C)(C)C)cc1Cl
Temperature: 70 °C
Reaction time: 16 h
Yield: 71.9 %

Procedure:
To a solution of (2-methylcyclohexyl)methanol (1.28 g, 9.99 mmol) in anhydrous dimethylsulfoxide (20 mL) was added cesium carbonate (5.87 g, 18.06 mmol) and tert-butyl 5-chloro-2,4-difluorobenzoate (2.23 g, 8.96 mmol). The reaction mixture was stirred at 70° C. for 16 hours; cooled to ambient temperature and acidified to pH=1 with 5% aqueous hydrochloric acid solution and extracted with ethyl acetate (2×15 mL), the combined organics were washed with brine (15 mL); dried over anhydrous sodium sulfate; filtered and concentrated in vacuo. Purification of the residue by column chromatography (0 to 10% ethyl acetate in hexanes) afforded the title compound (2.30 g, 72%); MS (ES+) m/z 303.2, 301.2 (M−54); MS (ES−) m/z 301.2, 299.2 (M−56).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([N:8]=[CH:9][C:10]2[CH:15]=[CH:14][C:13](OC)=[C:12](F)[CH:11]=2)[CH:5]=[C:4]([Cl:19])[C:3]=1[N:20]=[CH:21][N:22]([CH3:24])[CH3:23].[F:25]C1C=CC=CC=1C=O.C(O)C.CCOCC>CCCCCC>[Cl:1][C:2]1[CH:7]=[C:6]([N:8]=[CH:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[F:25])[CH:5]=[C:4]([Cl:19])[C:3]=1[N:20]=[CH:21][N:22]([CH3:24])[CH3:23]
Reactant: O=Cc1ccccc1F
Reactant: COc1ccc(C=Nc2cc(Cl)c(N=CN(C)C)c(Cl)c2)cc1F
Solvent: CCO
Solvent: CCCCCC
Solvent: CCOCC
Product: CN(C)C=Nc1c(Cl)cc(N=Cc2ccccc2F)cc1Cl

Procedure:
A mixture of 9.3 g. of N'-(4-amino-2,6-dichlorophenyl)-N,N-dimethylformamidine (Example 9) and 5.0 g. of o-fluorobenzaldehyde in 25 ml. of absolute ethanol is refluxed for 18 hours. The solution is evaporated in vacuo to provide a syrup. The syrup is dissolved in 50 ml. of ether and n-hexane is added to 500 ml. The solution is cooled and filtered. The filtrate is evaporated to 100 ml. to precipitate the product. The product is collected by filtration and washed with n-hexane to give 7.4 g. of the desired product as bright yellow crystals, m.p. 79°-81° C.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][C:7]([C:11]3([C:14]4[N:18]5[N:19]=[C:20]([C:23]6[CH:31]=[CH:30][C:26]([C:27](O)=[O:28])=[CH:25][CH:24]=6)[CH:21]=[N:22][C:17]5=[N:16][N:15]=4)[CH2:13][CH2:12]3)=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.Cl.[NH2:33][C@@H:34]([C:42]([CH3:45])([CH3:44])[CH3:43])[C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[CH3:43][C:42]([CH3:45])([CH3:44])[C@H:34]([NH:33][C:27](=[O:28])[C:26]1[CH:25]=[CH:24][C:23]([C:20]2[CH:21]=[N:22][C:17]3[N:18]([C:14]([C:11]4([C:7]5[CH:6]=[C:5]6[C:10](=[CH:9][CH:8]=5)[N:1]=[CH:2][CH:3]=[CH:4]6)[CH2:13][CH2:12]4)=[N:15][N:16]=3)[N:19]=2)=[CH:31][CH:30]=1)[C:35]([O:37][C:38]([CH3:39])([CH3:41])[CH3:40])=[O:36]
Reactant: CC(C)(C)OC(=O)[C@@H](N)C(C)(C)C
Reactant: O=C(O)c1ccc(-c2cnc3nnc(C4(c5ccc6ncccc6c5)CC4)n3n2)cc1
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC(=O)[C@@H](NC(=O)c1ccc(-c2cnc3nnc(C4(c5ccc6ncccc6c5)CC4)n3n2)cc1)C(C)(C)C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of 4-[3-(1-quinolin-6-ylcyclopropyl)[1,2,4]triazolo[4,3-b][1,2,4]triazin-6-yl]benzoic acid (40 mg, 0.10 mmol), tert-butyl (2S)-2-amino-3,3-dimethylbutanoate hydrochloride (26 mg, 0.12 mmol), benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (45.5 mg, 0.103 mmol), and N,N-diisopropylethylamine (60 μL, 0.34 mmol) in methylene chloride (1.5 mL) was stirred at RT overnight. The mixture was diluted with DCM, and washed with saturated NaHCO3 solution, water and brine, dried over Na2SO4, filtered, and concentrated to yield desired product which was directly used in the next step without further purification.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:22]=[C:23]([CH3:34])[C:24]=1[N:25]1[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[N:26]1)[O:5][CH:6]([CH:16]1[CH2:19][C:18]([CH3:21])([CH3:20])[CH2:17]1)[C:7]1[CH:15]=[CH:14][C:10]([C:11]([OH:13])=O)=[CH:9][CH:8]=1.Cl.[NH2:36][CH2:37][CH2:38][C:39]([O:41][CH2:42][CH3:43])=[O:40].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>O1CCCC1>[CH3:1][C:2]1[CH:3]=[C:4]([CH:22]=[C:23]([CH3:34])[C:24]=1[N:25]1[CH:29]=[C:28]([C:30]([F:32])([F:31])[F:33])[CH:27]=[N:26]1)[O:5][CH:6]([CH:16]1[CH2:19][C:18]([CH3:21])([CH3:20])[CH2:17]1)[C:7]1[CH:15]=[CH:14][C:10]([C:11]([NH:36][CH2:37][CH2:38][C:39]([O:41][CH2:42][CH3:43])=[O:40])=[O:13])=[CH:9][CH:8]=1
Reactant: CCOC(=O)CCN
Reactant: Cc1cc(OC(c2ccc(C(=O)O)cc2)C2CC(C)(C)C2)cc(C)c1-n1cc(C(F)(F)F)cn1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: CCOC(=O)CCNC(=O)c1ccc(C(Oc2cc(C)c(-n3cc(C(F)(F)F)cn3)c(C)c2)C2CC(C)(C)C2)cc1
Reaction time: 1 h
Yield: 80.2 %

Procedure:
Tetrahydrofuran (1.2 mL) was added to a vial containing 4-((3,5-dimethyl-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenoxy)(3,3-dimethylcyclobutyl)methyl)benzoic acid (115 mg, 0.240 mmol), ethyl 3-aminopropanoate hydrochloride (74.7 mg, 0.490 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (185 mg, 0.490 mmol). Diisopropylethylamine (0.210 mL, 1.22 mmol) was then added. The reaction was stirred for 1 h, and was then concentrated. Purification by column chromatography (0-50% ethyl acetate in heptane) afforded ethyl 3-(4-((3,5-dimethyl-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenoxy)(3,3-dimethylcyclobutyl)methyl)benzamido)propanoate (110 mg, 39% yield) as an oil. 1H NMR (400 MHz, CDCl3) δ 7.87 (s, 1H), 7.71 (d, J=8.6 Hz, 2H), 7.64 (s, 1H), 7.36 (d, J=8.2 Hz, 2H), 6.81 (t, J=4.8 Hz, 1H), 6.57 (s, 2H), 5.00 (d, J=6.8 Hz, 1H), 4.17 (q, J=7.2 Hz, 2H), 3.71 (q, J=6.1 Hz, 2H), 2.57-2.74 (m, 3H), 1.87-1.92 (m, 7H), 1.80-1.87 (m, 1H), 1.72-1.80 (m, 1H), 1.59-1.68 (m, 1H), 1.21-1.35 (m, 3H), 1.13 (s, 3H), 1.10 (s, 3H). MS (M+1): 572.3.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:21]=[CH:20][C:19]([NH:22][C:23](=O)[CH2:24][O:25][C:26]2[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][C:27]=2[Cl:33])=[CH:18][CH:17]=1.Cl.[OH-].[Na+]>O1CCCC1>[Cl:33][C:27]1[CH:28]=[C:29]([Cl:32])[CH:30]=[CH:31][C:26]=1[O:25][CH2:24][CH2:23][NH:22][C:19]1[CH:20]=[CH:21][C:16]([O:15][C:6]2[C:5]3[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=3)[N:9]=[CH:8][CH:7]=2)=[CH:17][CH:18]=1
Reactant: COc1cc2nccc(Oc3ccc(NC(=O)COc4ccc(Cl)cc4Cl)cc3)c2cc1OC
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: COc1cc2nccc(Oc3ccc(NCCOc4ccc(Cl)cc4Cl)cc3)c2cc1OC
Temperature: 0 °C
Yield: 80.2 %

Procedure:
N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]phenyl}-2-(2,4-dichlorophenoxy)acetamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (156 mg, yield 80%).
Reaction SMILES: [F:1][C:2]1[C:3](=[O:9])[NH:4][C:5](=[O:8])[NH:6][CH:7]=1.[CH3:10][N:11]=[C:12]=[O:13]>CS(C)=O>[F:1][C:2]1[C:3](=[O:9])[NH:4][C:5](=[O:8])[N:6]([C:12](=[O:13])[NH:11][CH3:10])[CH:7]=1
Reactant: CN=C=O
Reactant: O=c1[nH]cc(F)c(=O)[nH]1
Solvent: CS(C)=O
Product: CNC(=O)n1cc(F)c(=O)[nH]c1=O
Yield: 86.1 %

Procedure:
10.4 g. (0.08 mole) of 5-fluorouracil and 10.0 g. (0.176 mole) of methyl isocyanate were mixed in 100 ml. of dimethyl sulfoxide and stirred at room temperature. Dimethyl sulfoxide and excess methyl isocyanate were removed from the reaction mixture by distillation. The resultant residue was washed with chloroform and dried in a vacuum oven to give 15.8 g. (86.1% yield) of 5-fluoro-1-methylcarbamoyluracil. The product was recrystallized from ethyl acetate and there were obtained white crystals melting at 277° C.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[CH3:7][O:8][C:9]1[CH:26]=[C:25]([CH:27]=[CH:28][N+:29]([O-])=O)[CH:24]=[CH:23][C:10]=1[O:11][CH2:12][C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=[CH:15][CH:14]=1.[OH-].[Na+]>O1CCCC1>[CH3:7][O:8][C:9]1[CH:26]=[C:25]([CH2:27][CH2:28][NH2:29])[CH:24]=[CH:23][C:10]=1[O:11][CH2:12][C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=[CH:15][CH:14]=1
Reactant: COc1cc(C=C[N+](=O)[O-])ccc1OCc1cccc2ccccc12
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: COc1cc(CCN)ccc1OCc1cccc2ccccc12
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
10 g of lithium aluminium hydride are placed in 200 ml of tetrahydrofuran; the mixture is stirred at room temperature. 25.8 g of 1-[2-methoxy-4-(2-nitro-vinyl)-phenoxymethyl]-naphthalene dissolved in 300 ml of tetrahydrofuran are added dropwise thereto over a period of 90 minutes. The reaction mixture is heated at reflux for 4 hours. After cooling, 40 ml of 1 N sodium hydroxide solution are cautiously added dropwise, external cooling being effected using an ice bath. When the addition is complete, the reaction mixture is stirred, without cooling, for one hour, then filtered with suction over Celite and washed with a small amount of tetrahydrofuran. The filtrate is dried over potassium carbonate and concentrated by evaporation, yielding 2-[3-methoxy-4-(naphthalen-1-ylmethoxy)-phenyl]-ethylamine in the form of a brown oil.
Reaction SMILES: Br[C:2](=[CH2:18])[CH2:3][NH:4][C:5]1[CH:10]=[C:9]([C:11]2[CH:12]=[N:13][C:14]([CH3:17])=[CH:15][CH:16]=2)[N:8]=[CH:7][N:6]=1.CC1(C)C(C)(C)OB([C:27]2[CH:32]=[CH:31][N:30]=[C:29]3[O:33][CH2:34][CH2:35][O:36][C:28]=23)O1.C([O-])([O-])=O.[Na+].[Na+]>CS(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[O:36]1[C:28]2[C:29](=[N:30][CH:31]=[CH:32][C:27]=2[C:2](=[CH2:18])[CH2:3][NH:4][C:5]2[CH:10]=[C:9]([C:11]3[CH:12]=[N:13][C:14]([CH3:17])=[CH:15][CH:16]=3)[N:8]=[CH:7][N:6]=2)[O:33][CH2:34][CH2:35]1
Reactant: C=C(Br)CNc1cc(-c2ccc(C)nc2)ncn1
Reactant: CC1(C)OB(c2ccnc3c2OCCO3)OC1(C)C
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: CS(C)=O
Product: C=C(CNc1cc(-c2ccc(C)nc2)ncn1)c1ccnc2c1OCCO2
Temperature: 100 °C
Reaction time: 1 h

Procedure:
As shown in step 8-i of Scheme 8, N-(2-bromoallyl)-6-(6-methyl-3-pyridyl)pyrimidin-4-amine (240 mg, 0.7792 mmol, Compound 2027; which was prepared by reacting 4-chloro-6-(6-methylpyridin-3-yl)pyrimidine with 2-bromoprop-2-en-1-amine under basic conditions), 8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-[1,4]dioxino[2,3-b]pyridine (287.0 mg, 1.091 mmol), and Na2CO3 (1.169 mL of 2 M, 2.338 mmol) were stirred in DMSO (5.945 mL). Pd(dppf)Cl2 (63.63 mg, 0.07792 mmol) was added and the reaction mixture stirred at 100° C. for 1 hour, then at RT for 16 hours. After this time the reaction mixture was partitioned between EtOAc and water, the organics dried over Na2SO4, filtered, and the volatiles removed under reduced pressure. The residue was dissolved in DCM and purified by medium pressure silica gel chromatography (20-100% EtOAc/hexanes, then 0-10% MeOH/DCM) to produce N-(2-(2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-8-yl)allyl)-6-(6-methylpyridin-3-yl)pyrimidin-4-amine (Compound 2028) as yellow oil: LCMS=362.37 (M+H). This material was used as is in subsequent reactions.
Reaction SMILES: [CH:1]([C:3]([CH3:5])=[O:4])=[CH2:2].[Cl-].[Al+3].[Cl-].[Cl-].C(Cl)Cl.[CH2:13]=[CH:14][C:15]([Cl:17])=[CH2:16]>O>[Cl:17][C:15]1[CH2:14][CH2:13][CH:1]([C:3](=[O:4])[CH3:5])[CH2:2][CH:16]=1
Reactant: C=CC(=C)Cl
Reactant: C=CC(C)=O
Agent: [Al+3]
Agent: [Cl-]
Solvent: O
Solvent: ClCCl
Product: CC(=O)C1CC=C(Cl)CC1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of 98.1 parts of methyl vinyl ketone, 187 parts of anhydrous aluminum chloride and 1980 parts of methylene chloride was added 123 parts of chloroprene and the mixture was stirred at 25° C. for three hours and left standing for another 16 hours. Water was added to the reaction mixture and the organic layer was washed with 5% hydrochloric acid. Distillation gave a center cut of 61 parts of 1-chloro-4-acetyl-cyclohexene (125°-6° C./20 mm Hg). Reference: A. A. Petrov and N. P. Sopov, CA 42, 1910h (1948).
Reaction SMILES: Br[C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][CH:10]=2)[N:3]=1.[I:16][C:17]1[N:18]=[CH:19][NH:20][CH:21]=1>>[Cl:15][C:12]1[CH:13]=[CH:14][C:9]([C:4]2[CH:5]=[C:6]([CH3:8])[CH:7]=[C:2]([N:20]3[CH:21]=[C:17]([I:16])[N:18]=[CH:19]3)[N:3]=2)=[CH:10][CH:11]=1
Reactant: Cc1cc(Br)nc(-c2ccc(Cl)cc2)c1
Reactant: Ic1c[nH]cn1
Product: Cc1cc(-c2ccc(Cl)cc2)nc(-n2cnc(I)c2)c1

Procedure:
The title compound was prepared from 2-bromo-6-(4-chloro-phenyl)-4-methyl-pyridine (example A.22) (0.94 g, 3.0 mmol) and commercially available 4-iodo-imidazole (0.71 g, 3.3 mmol) according to the general procedure IVa. Obtained as a yellow gum (0.213 g, 18%). MS (ISP) 396.0 [(M+H)+].
Reaction SMILES: [CH3:1][CH:2]([CH:8]=[CH2:9])[CH2:3][CH2:4][CH2:5][CH2:6][OH:7].P(=O)(O)(O)O>>[CH2:8]([C:2]1([CH3:1])[CH2:3][CH2:4][CH2:5][CH2:6][O:7]1)[CH3:9]
Reactant: C=CC(C)CCCCO
Agent: O=P(O)(O)O
Product: CCC1(C)CCCCO1

Procedure:
1.8 grams of 5-methyl-6-hepten-1-ol (containing 5.4 percent 5-methyl-5-hepten-1-ol and 2.4 percent impurities) was reacted with 18 cc of 85 percent phosphoric acid at room temperature for 3.5 hours. Then the solution was worked up using the procedure of Example II. The v.p.c. showed the following to be present:
Reaction SMILES: C1(=[O:8])NCCCCC1.[CH2:9]([C:11]([CH2:16][OH:17])([CH2:14][OH:15])[CH2:12]C)[OH:10].O>>[OH:10][CH2:9][C:11]([CH2:16][OH:17])([CH2:14][OH:15])[CH2:12][OH:8]
Reactant: CCC(CO)(CO)CO
Reactant: O=C1CCCCCN1
Solvent: O
Product: OCC(CO)(CO)CO

Procedure:
Similar viscosities are obtained by initially heating the polyalcohols (a) to (d) with polyphosphoric acid (= phosphoric acid dehydrated above 200° C.), resulting once again in the formation of acid semi-esters and diester mixtures through cleavage of the anhydridic phosphorus-oxygen-phosphorus bond. These acid semi-ester and di-ester mixtures are mixed with the multicomponent mixture of 1 mol of ε-caprolactam, 1 mol of trimethylol propane and 1 mol of water.
Reaction SMILES: [CH2:1]([OH:7])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].P(Cl)(Cl)(Cl)=O.O.O.Cl[Sn]Cl.[CH3:18][O:19][C:20]1[CH:21]=[CH:22][CH:23]=[C:24]2[C:29]=1[C:28](=[O:30])[CH:27]=[CH:26][C:25]2=O.Cl>C(#N)C>[CH2:1]([O:7][C:25]1[C:24]2[C:29](=[C:20]([O:19][CH3:18])[CH:21]=[CH:22][CH:23]=2)[C:28]([OH:30])=[CH:27][CH:26]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: CCCCCCO
Reactant: COc1cccc2c1C(=O)C=CC2=O
Agent: Cl
Agent: Cl[Sn]Cl
Solvent: CC#N
Solvent: O
Solvent: O=P(Cl)(Cl)Cl
Product: CCCCCCOc1ccc(O)c2c(OC)cccc12

Procedure:
10 ml of hexyl alcohol and 50 ml of acetonitrile were placed in a 1 l three-necked flask, and 12.8 g of phosphorus oxychloride was dropwisely added thereto under cooling with ice while stirring. Thereafter, 9.5 g of SnCl2.2H2O was added to the reaction mixture at room temperature. Then, 7.5 g of 8-methoxy-1,4-naphthoquinone was added to the reaction mixture at room temperature. The reaction mixture was refluxed for 2 hours on steam bath. The reaction mixture was poured into 1.2 l of diluted hydrochloric acid and extracted with 500 ml of ethyl acetate. The ethyl acetate solution was washed with water, dried with MgSO4 overnight, and concentrated under reduced pressure to obtain 9 g of oily substance. The oily substance was purified by column chromatography using a mixed solvent of n-hexane and ethyl acetate and, then, recrystallized from benzene to obtain 6 g of white crystals having a melting point of 105° to 107° C.
Reaction SMILES: [OH-].[Na+].[CH3:3][O:4][C:5]1[CH:6]=[C:7]([N:13]([CH2:23][C:24]([O:26]CC)=[O:25])[S:14]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)(=[O:16])=[O:15])[CH:8]=[CH:9][C:10]=1[O:11][CH3:12].Cl>O1CCCC1>[CH3:3][O:4][C:5]1[CH:6]=[C:7]([N:13]([CH2:23][C:24]([OH:26])=[O:25])[S:14]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)(=[O:16])=[O:15])[CH:8]=[CH:9][C:10]=1[O:11][CH3:12]
Reactant: CCOC(=O)CN(c1ccc(OC)c(OC)c1)S(=O)(=O)c1ccccc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: COc1ccc(N(CC(=O)O)S(=O)(=O)c2ccccc2)cc1OC
Temperature: 25 °C
Reaction time: 2 h
Yield: 99.3 %

Procedure:
A 20 ml portion of 1 M sodium hydroxide aqueous solution was added to a tetrahydrofuran solution (20 ml) of 2.48 g of ethyl [(3,4-dimethoxyphenyl)(phenylsulfonyl)amino]acetate and stirred at room temperature for 2 hours. This was acidified by adding 1 M hydrochloric acid and then layer separation operation was carried out by adding chloroform thereto, and the organic layer was washed with saturated brine, dried with anhydrous sodium sulfate and then concentrated under a reduced pressure to obtain 2.28 g of [(3,4-dimethoxyphenyl)(phenylsulfonyl)amino]acetic acid as a pale yellow foamy substance.
Reaction SMILES: [CH3:1][C@@H:2]([C@@H:33]([OH:35])[CH3:34])[C@@H:3]1[O:5][C@H:4]1[CH2:6][C@@H:7]1[C@@H:12]([OH:13])[C@@H:11]([OH:14])[C@H:10]([CH2:15]/[C:16](/[CH3:32])=[CH:17]/[C:18]([O:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][C:29]([OH:31])=[O:30])=[O:19])[O:9][CH2:8]1.[OH-].[K+].[Cl-].[Ca+2:39].[Cl-].[CH3:41][C@@H:42]([C@@H:73]([OH:75])[CH3:74])[C@@H:43]1[O:45][C@H:44]1[CH2:46][C@@H:47]1[C@@H:52]([OH:53])[C@@H:51]([OH:54])[C@H:50]([CH2:55]/[C:56](/[CH3:72])=[CH:57]/[C:58]([O:60][CH2:61][CH2:62][CH2:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][C:69]([OH:71])=[O:70])=[O:59])[O:49][CH2:48]1.[K]>CO>[CH3:1][C@H:2]([C@H:3]1[C@H:4]([CH2:6][C@H:7]2[CH2:8][O:9][C@@H:10]([CH2:15]/[C:16](/[CH3:32])=[CH:17]/[C:18]([O:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][C:29]([O-:31])=[O:30])=[O:19])[C@H:11]([OH:14])[C@@H:12]2[OH:13])[O:5]1)[C@H:33]([CH3:34])[OH:35].[CH3:41][C@H:42]([C@H:43]1[C@H:44]([CH2:46][C@H:47]2[CH2:48][O:49][C@@H:50]([CH2:55]/[C:56](/[CH3:72])=[CH:57]/[C:58]([O:60][CH2:61][CH2:62][CH2:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][C:69]([O-:71])=[O:70])=[O:59])[C@H:51]([OH:54])[C@@H:52]2[OH:53])[O:45]1)[C@H:73]([CH3:74])[OH:75].[Ca+2:39]
Reactant: C/C(=C\C(=O)OCCCCCCCCC(=O)O)C[C@@H]1OC[C@H](C[C@@H]2O[C@H]2[C@@H](C)[C@H](C)O)[C@@H](O)[C@H]1O
Agent: [Ca+2]
Agent: [Cl-]
Agent: [K+]
Solvent: CO
Product: C/C(=C\C(=O)OCCCCCCCCC(=O)[O-])C[C@@H]1OC[C@H](C[C@@H]2O[C@H]2[C@@H](C)[C@H](C)O)[C@@H](O)[C@H]1O
Temperature: 24.5 °C

Procedure:
Pseudomonic acid (220 g) was dissolved in methanol (210 ml) kept at 25-27° C. Separately, potassium hydroxide (27.9 g) was dissolved in methanol (154 ml). Also separately, calcium chloride (24.39 g) was dissolved in methanol (133 ml). The potassium hydroxide solution was added to the pseudomonic acid solution until obtaining a pH=9.4-9.5 (147 ml of potassium hydroxide solution was added.). The calcium chloride solution was then added to the mupirocin potassium solution until reaching a pH=7.6-7.7 (128 ml of calcium chloride solution was added.). The solution was stirred at 24-25° C. for an hour. Potassium chloride was filtered, and the solution was labeled Solution B. Solution B (25 ml) was added to diisopropyl-ether (250 ml) at (−7)° C. while stirring. Solid amorphous mupirocin calcium precipitated from the solution, and was stirred at −7° C. for 3 h. The solid product was filtered and washed with cold diisoprpyl-ether (10 ml). The product was dried in a fluidized bed dryer for 6 hours at 35° C., and then in a vacuum oven for 12 h at 35° C.
Reaction SMILES: [Cl-].[CH3:2][O:3]C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[H-].[Na+].[F:26][C:27]1[CH:28]=[CH:29][C:30]([O:35][CH3:36])=[C:31]([CH:34]=1)[CH:32]=O.[Cl-].[NH4+].OS(O)(=O)=O>C1COCC1.CC(C)=O>[F:26][C:27]1[CH:28]=[CH:29][C:30]([O:35][CH3:36])=[C:31]([CH2:32][CH:2]=[O:3])[CH:34]=1
Reactant: COc1ccc(F)cc1C=O
Reactant: COC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=S(=O)(O)O
Agent: [Cl-]
Agent: [H-]
Solvent: C1CCOC1
Solvent: CC(C)=O
Product: COc1ccc(F)cc1CC=O
Temperature: 0 °C
Reaction time: 12 h
Yield: 60.2 %

Procedure:
To a suspension of methoxymethyltriphenylphosphonium chloride (10.0 g, 30.0 mmol) in THF (30 mL) under Ar was added NaH (60% in mineral oil, 1.2 g, 30 mmol) and then heated to reflux for 1 h. The orange colored suspension was cooled to 0° C. and 5-fluoro-2-methoxybenzaldehyde (4.2 g, 26.0 mmol) was added and the mixture was stirred for 12 h at room temperature. The reaction mixture was then poured into a separatory funnel containing ammonium chloride aqueous solution (sat. NH4Cl/H2O, 1:1, v:v, 100 mL). The organic material was extracted with ethyl acetate (3×80 mL) and the combined organic layers were washed with brine (60 mL) and dried over Na2SO4. The solvent was then removed in vacuo and the crude product (2a) obtained was dissolved in acetone (50 mL). H2SO4 (1 M, 1.5 mL) was then added and the mixture obtained was heated to reflux for 6 h while stirring. The reaction was then cooled to room temperature and the solvent was removed in vacuo to obtain the crude product that was then purified by flash column chromatography (Rf=0.15, EtOAc/Hexane, 10:90, v:v) to afford the product (2.63 g, 66%) as an oil: 1H NMR (CDCl3, 500 MHz): δ 9.68 (s, 1 H), 6.97 (dt, J=3.1, 8.7 Hz, 1 H), 6.89 (dd, J=3.1, 8.7 Hz, 1 H), 6.83 (dd, J=4.3, 8.7 Hz, 1 H), 3.80 (s, 3 H), 3.63 (d, J=1.7 Hz, 2 H).