Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:13](=[O:15])[CH3:14])[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].[Br:16][C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[NH:22][CH:21]=[C:20]2[CH:26]=O>>[Br:16][C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[NH:22][CH:21]=[C:20]2/[CH:26]=[CH:14]/[C:13]([C:5]1[CH:6]=[C:7]([O:11][CH3:12])[C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=1)=[O:15]
Reactant: COc1cc(C(C)=O)cc(OC)c1OC
Reactant: O=Cc1c[nH]c2ccc(Br)cc12
Product: COc1cc(C(=O)/C=C/c2c[nH]c3ccc(Br)cc23)cc(OC)c1OC
Yield: 65.7 %

Procedure:
Substantially the same procedure as in Example 12 was repeated using 3',4',5'-trimethoxyacetophenone (2.1 g) and 5-bromoindole-3-carboxaldehyde (2.24 g) except that the obtained crystals were recrystallized from ethyl acetate, to give Compound 31 (2.73 g).
Reaction SMILES: [CH2:1]([N:8]1[CH:13]=[CH:12][C:11]([O:14]CC2C=CC=CC=2)=[C:10](I)[C:9]1=[O:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[CH2:33]([Si:35]([C:40]#[C:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)([CH2:38][CH3:39])[CH2:36][CH3:37])[CH3:34]>CN(C=O)C>[CH2:1]([N:8]1[CH:13]=[CH:12][C:11](=[O:14])[C:10]2[C:41]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)=[C:40]([Si:35]([CH2:38][CH3:39])([CH2:33][CH3:34])[CH2:36][CH3:37])[O:23][C:9]1=2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC[Si](C#Cc1ccccc1)(CC)CC
Reactant: O=c1c(I)c(OCc2ccccc2)ccn1Cc1ccccc1
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CC[Si](CC)(CC)c1oc2c(c1-c1ccccc1)c(=O)ccn2Cc1ccccc1
Temperature: 110 °C
Reaction time: 12 h

Procedure:
A 250-ml round bottom flask was charged with 1-benzyl-4-benzyloxy-3-iodo-2-pyridone (6.00 g, 14.40 mmol), dichloro[1,1-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (1.18 g, 1.44 mmol), DMF (60 mL), Hunig's base (3 mL, 17.30 mmol), triethylsilyl phenylacetylene (9.34 g, 43.10 mmol). The system was evacuated and purged with N2 three times, and the reaction was stirred at 110° C. for 12 hrs. The reaction mixture was diluted with EtOAc and washed with water. The organic layer was dried over Na2SO4 and the solvent was removed. The residue was purified by silica gel column chromatography, eluting with 50/50/1, EtOAc/Hexane/MeOH, to give 7-benzyl-3-phenyl-2-(triethylsily)furo[2,3-b]pyridine-4(7H)-one as a solid. MS (MH+) 416.0; Calculated 415 for C26H29NO2Si.
Reaction SMILES: [CH3:1][C:2]1[NH:7][C:6](=[O:8])[C:5]([C:9]#[N:10])=[C:4]([CH:11]([CH3:13])[CH3:12])[CH:3]=1.[B-](F)(F)(F)[F:15].[B-](F)(F)(F)F.C1[N+]2(CCl)CC[N+](F)(CC2)C1>CC#N>[F:15][C:3]1[C:4]([CH:11]([CH3:13])[CH3:12])=[C:5]([C:9]#[N:10])[C:6](=[O:8])[NH:7][C:2]=1[CH3:1]
Reactant: F[B-](F)(F)F
Reactant: Cc1cc(C(C)C)c(C#N)c(=O)[nH]1
Agent: F[N+]12CC[N+](CCl)(CC1)CC2
Solvent: CC#N
Product: Cc1[nH]c(=O)c(C#N)c(C(C)C)c1F
Temperature: 50 °C
Reaction time: 3 h
Yield: 36.3 %

Procedure:
To a stirred solution of 6-methyl-2-oxo-4-(propan-2-yl)-1,2-dihydropyridine-3-carbonitrile (225 mg, 1.277 mmol) in MeCN (6 mL) was added Selectfluor (620 mg, 1.75 mmol). The reaction mixture was stirred at 50° C. for 3 h. After cooling to 23° C., the reaction mixture was concentrated in vacuo. The residue was purified by column chromatography (50% to 100% EtOAc-heptane to obtain the titled compound (90 mg, 36%). 1H NMR (400 MHz, CDCl3) δ ppm 3.39 (m, 1H), 2.44 (d, J=3.1 Hz, 3H), 1.41 (dd, J=7.0, 3.1 Hz, 6H); LCMS E-S (M+H)=195.2.
Reaction SMILES: [ClH:1].[N+:2]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[CH2:10]C(N)[CH2:8]2)([O-:4])=[O:3].C(N([CH2:20][CH3:21])CC)C.[Br-].O.[CH3:24][N:25]([CH:27]=O)C>>[ClH:1].[N+:2]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[CH2:10][CH:24]([NH:25][CH2:27][C:21]1[CH:20]=[CH:12][CH:13]=[CH:5][CH:6]=1)[CH2:8]2)([O-:4])=[O:3]
Reactant: CN(C)C=O
Reactant: NC1Cc2ccc([N+](=O)[O-])cc2C1
Reactant: CCN(CC)CC
Agent: Cl
Agent: [Br-]
Solvent: O
Product: O=[N+]([O-])c1ccc2c(c1)CC(NCc1ccccc1)C2
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To 5-nitro-2-aminoindane hydrochloride (3.00 g, 14.00 mmol) in DMF (60 ml) was added triethylamine (4.07 ml, 29.40 mmol) followed by henzyl bromide (1.74 ml, 14.68 mmol). The mixture was warmed to room temperature, stirred for 1 hr, dumped into water (200 ml), and extracted with ethyl acetate (3×50 ml). The combined extracts were washed with water, dried over magnesium sulfate, filtered through a small plug of silica gel and reduced to a syrup. The sub-titled compound was isolated as the hydrochloride salt: (2.29 g, 54%); m.p. dec 266° C.
Reaction SMILES: [CH:1]1([Mg]Br)[CH2:3][CH2:2]1.[F:6][C:7]1[CH:14]=[C:13]([N:15]2[CH2:19][CH2:18][N:17]([C:20]3[CH:21]=[N:22][CH:23]=[CH:24][C:25]=3[CH3:26])[C:16]2=[O:27])[CH:12]=[CH:11][C:8]=1[CH:9]=[O:10].CO>C1COCC1.C(Cl)(Cl)Cl>[CH:1]1([CH:9]([OH:10])[C:8]2[CH:11]=[CH:12][C:13]([N:15]3[CH2:19][CH2:18][N:17]([C:20]4[CH:21]=[N:22][CH:23]=[CH:24][C:25]=4[CH3:26])[C:16]3=[O:27])=[CH:14][C:7]=2[F:6])[CH2:3][CH2:2]1
Reactant: Br[Mg]C1CC1
Reactant: Cc1ccncc1N1CCN(c2ccc(C=O)c(F)c2)C1=O
Solvent: C1CCOC1
Solvent: CO
Solvent: ClC(Cl)Cl
Product: Cc1ccncc1N1CCN(c2ccc(C(O)C3CC3)c(F)c2)C1=O
Temperature: 25 °C
Reaction time: 3 h
Yield: 99.41 %

Procedure:
A 0.5M solution of cyclopropyl magnesium bromide in THF (2.4 mL, 1.170 mmol) was added dropwise to 2-fluoro-4-[3-(4-methyl-pyridin-3-yl)-2-oxo-imidazolidin-1-yl]-benzaldehyde (I-121a: 175 mg, 0.585 mmol) in dry THF (10 mL) at 0° C. under nitrogen atmosphere. The resulting mixture was stirred at room temperature for 3 hours. The reaction was monitored by TLC (5% MeOH in CHCl3). The reaction mixture was quenched with aqueous NH4Cl solution and the THF layer was concentrated. The aqueous layer was extracted with ethylacetate. The organic layer was dried over Na2SO4 and concentrated to afford the crude product. Purification by column chromatography on silica gel (3% MeOH in CHCl3), followed by hexane wash, afforded 200 mg of the product (99.41% yield).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([I:9])[CH:3]=1.[Cl:10][C:11]1[CH:18]=[CH:17][C:14]([CH2:15]Br)=[C:13]([F:19])[CH:12]=1.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:15][C:14]2[CH:17]=[CH:18][C:11]([Cl:10])=[CH:12][C:13]=2[F:19])=[C:4]([I:9])[CH:3]=1
Reactant: Fc1cc(Cl)ccc1CBr
Reactant: Oc1ccc(Cl)cc1I
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: Fc1cc(Cl)ccc1COc1ccc(Cl)cc1I
Temperature: 22.5 °C

Procedure:
To a solution of 4-chloro-2-iodophenol (899 g, 1 eq) and 4-chloro-2-fluorobenzyl bromide (700 g, 1.02 eq) in acetone (8.1 L) was added anhydrous potassium carbonate (926 g). The stirred suspension was then heated to reflux for 30 minutes. 0.12% starting material was observed by HPLC. The product mixture was cooled to 20-25° C. HPLC showed complete consumption of starting material. Inorganic material was then removed by filtration. The residue was washed with acetone (3.6 L) and the combined filtrate and washes were concentrated to 5 vol by atmospheric distillation. Isooctane (4.5 L) was added and reconcentrated to 5 vol by atmospheric distillation. This was repeated once more. The solution was then cooled from 85° C. to 75° C. No precipitation occurred. The batch was then cooled further to 55° C. over 30 minutes, leading to the formation of an immobile suspension. The batch was re-heated to 65° C. which thinned the suspension. The batch was then cooled to 55° C. over 30 minutes. This caused a more controlled precipitation with a mobile suspension.
Reaction SMILES: [OH-].[K+].CO[C:5]([C:12]([F:15])([F:14])[F:13])=[CH:6][C:7]([O:9]CC)=O.[C:16]([O:20][CH3:21])(=[O:19])[CH2:17][SH:18].S(=O)(=O)(O)O>CO>[OH:9][C:7]1[CH:6]=[C:5]([C:12]([F:13])([F:14])[F:15])[S:18][C:17]=1[C:16]([O:20][CH3:21])=[O:19]
Reactant: CCOC(=O)C=C(OC)C(F)(F)F
Reactant: COC(=O)CS
Agent: O=S(=O)(O)O
Agent: [K+]
Agent: [OH-]
Solvent: CO
Product: COC(=O)c1sc(C(F)(F)F)cc1O
Temperature: 25 °C
Reaction time: 24 h
Yield: 64.9 %

Procedure:
A solution of 1M potassium hydroxide in methanol (30 ml) is added to a cooled mixture of 1A (4.6 g), methyl thioglycolate (2.46 g) and methanol (10 ml). The resulting reaction mixture was stirred for 24 hours at room temperature. Then the mixture was poured on ice and acidified with 6N sulfuric acid (pH=2). The mixture is extracted with diethyl ether twice. The combined organic phases were washed with water and dried. The mixture was concentrated and the residue is distilled under reduced pressure to yield the product as a clear liquid (3.4 g, 65%) with a boiling point of 42°-45° C. at 0.10 mm.
Reaction SMILES: FC(F)(F)S(O[CH2:7][C:8]([F:18])([F:17])[CH2:9][O:10][CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)(=O)=O.[C:21]1(=[O:31])[NH:25][C:24](=[O:26])[C:23]2=[CH:27][CH:28]=[CH:29][CH:30]=[C:22]12.[K]>CN(C)C=O>[F:17][C:8]([F:18])([CH2:7][N:25]1[C:24](=[O:26])[C:23]2=[CH:27][CH:28]=[CH:29][CH:30]=[C:22]2[C:21]1=[O:31])[CH2:9][O:10][CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1
Reactant: O=C1NC(=O)c2ccccc21
Reactant: O=S(=O)(OCC(F)(F)COC1CCCCO1)C(F)(F)F
Agent: [K]
Solvent: CN(C)C=O
Product: O=C1c2ccccc2C(=O)N1CC(F)(F)COC1CCCCO1
Temperature: 85 °C

Procedure:
A mixture of 2,2-difluoro-3-tetrahydropyranyloxypropyl trifluoromethanesulfonate (2.3 g, 7 mmol), potassium phthalimide (1.4 g, 7.7 mmol) and anhydrous dimethylformamide (50 ml) under nitrogen was stirred and heated at 85° C. overnight. After cooling, salts are filtered off, and the solvent was removed in uacuo. The residue was taken up in dichloromethane (100 ml), washed with 0.5M NaOH (30 ml) and brine. The organic phase was separated, dried over magnesium sulfate and concentrated. The desired compound 2,2-difluoro-3-phthalimido-1-tetrahydropyranyloxypropane was purified by flash chromatography on silica gel (ethyl acetate:hexane; 20:80) (2 g, 90%).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](O)=[O:7])=[C:4]([CH3:11])[CH:3]=1.ClCCl.C(Cl)(=O)C(Cl)=O.C[N:22](C=O)C>>[CH3:11][C:4]1[CH:3]=[C:2]([Cl:1])[CH:10]=[CH:9][C:5]=1[C:6]([NH2:22])=[O:7]
Reactant: CN(C)C=O
Reactant: Cc1cc(Cl)ccc1C(=O)O
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Product: Cc1cc(Cl)ccc1C(N)=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 89 %

Procedure:
A magnetically stirred mixture of acid 4-chloro-2-methylbenzoic acid (50 g, 0.29 mol), dichloromethane (200 mL), and 0.5 mL DMF was cooled in an ice-bath. The cooler was connected to a gas absorption trap. Oxalyl chloride (44.5 g, 0.35 mmol) was added dropwise in 1 h. The mixture was stirred at r.t. overnight during which time all solid dissolved. The solution was concentrated in vacuo and stripped with dichloromethane to remove excess oxalyl chloride. The residue was taken in THF (200 mL) and mechanically stirred in an ice-water bath. Aqueous 25% ammonia (100 mL) was added in 15 min, which resulted in the formation of a precipitate. The THF was removed with the rotavap and extra water (100 mL) was added. The suspension was stirred at r.t. overnight. The solid was collected by filtration and dried in vacuo to give 2-methyl-4-chlorobenzamide (43.7 g, yield 89%) that was used without purification in the next step.
Reaction SMILES: [Br:1]N1C(=O)CCC1=O.[CH3:9][O:10][C:11]1[C:16]2[N:17]=[C:18]([S:20][CH3:21])[O:19][C:15]=2[CH:14]=[CH:13][CH:12]=1>C(#N)C>[Br:1][C:14]1[C:15]2[O:19][C:18]([S:20][CH3:21])=[N:17][C:16]=2[C:11]([O:10][CH3:9])=[CH:12][CH:13]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: COc1cccc2oc(SC)nc12
Solvent: CC#N
Product: COc1ccc(Br)c2oc(SC)nc12
Reaction time: 18 h
Yield: 33.8 %

Procedure:
N-Bromosuccinimide (2.4 g) was added to a solution of 4-methoxy-2-methylsulfanylbenzooxazole (2.63 g) in acetonitrile (80 ml) and the mixture stirred for 18 hours. It was then partitioned between dichloromethane (200 ml) and water (200 ml). The organics were washed with water (200 ml), dried over magnesium sulphate, filtered and the solvent removed in vacuo. Purification by column chromatography on silica eluting with 10% ethyl acetate in heptane afforded the title compound as a white solid (1.25 g).
Reaction SMILES: [NH2:1][CH:2]1[N:8]=[C:7]([CH3:9])[C:6]2[CH:10]=[CH:11][CH:12]=[C:13]([N:14]([CH3:16])[CH3:15])[C:5]=2[N:4]([CH2:17][C:18]([N:20]2[CH2:26][CH:25]3[CH2:27][CH2:28][CH:22]([CH2:23][CH2:24]3)[CH2:21]2)=[O:19])[C:3]1=[O:29].[C:30]1([CH3:39])[CH:35]=[CH:34][CH:33]=[C:32]([N:36]=[C:37]=[O:38])[CH:31]=1.[ClH:40]>O1CCCC1.C(OCC)(=O)C>[ClH:40].[CH:25]12[CH2:24][CH2:23][CH:22]([CH2:28][CH2:27]1)[CH2:21][N:20]([C:18]([CH2:17][N:4]1[C:5]3[C:13]([N:14]([CH3:16])[CH3:15])=[CH:12][CH:11]=[CH:10][C:6]=3[C:7]([CH3:9])=[N:8][CH:2]([NH:1][C:37]([NH:36][C:32]3[CH:33]=[CH:34][CH:35]=[C:30]([CH3:39])[CH:31]=3)=[O:38])[C:3]1=[O:29])=[O:19])[CH2:26]2
Reactant: Cc1cccc(N=C=O)c1
Reactant: CC1=NC(N)C(=O)N(CC(=O)N2CC3CCC(CC3)C2)c2c1cccc2N(C)C
Agent: Cl
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CC1=NC(NC(=O)Nc2cccc(C)c2)C(=O)N(CC(=O)N2CC3CCC(CC3)C2)c2c1cccc2N(C)C
Temperature: 25 °C
Yield: 61.5 %

Procedure:
To a solution of (3RS)-3-amino-1-[(3-azabicyclo[3.2.2]non-3-yl)-carbonylmethyl]-5-methyl-9-(N,N-dimethylamino)-2,3-dihydro-1H-1,4-benzodiazepin-2-one (285 mg) in tetrahydrofuran (4 ml) was added dropwise 3-tolyl isocyanate (100 mg) under stirring at room temperature. The mixture was stirred at room temperature for 2 hours. Removal of the solvent in vacuo afforded a residue, which was triturated in diisopropyl ether and collected by filtration to give a white powder. To a solution of the powder in ethyl acetate was added 4N-hydrogen chloride in ethyl acetate (0.25 ml) under cooling. The mixture was evaporated in vacuo to dryness. The residue was washed with diisopropyl ether and collected by filtration to afford N-[(3RS)-1-(3-azabicyclo[3.2.2]non-3-yl)carbonylmethyl-5-methyl-9-(N,N-dimethylamino )-2,3-dihydro-2-oxo-1H-1,4-benzodiazepin-3-yl]-N′-(3-methylphenyl)urea hydrochloride (250 mg,61.5%) as a crystalline powder.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](O)=[O:7])=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12].[NH2:14]C(N)=O>ClC1C=CC=CC=1Cl.P(O)(O)O>[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH2:14])=[O:7])=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12]
Reactant: O=C(O)c1ccc(Cl)c([N+](=O)[O-])c1
Reactant: NC(N)=O
Agent: OP(O)O
Solvent: Clc1ccccc1Cl
Product: NC(=O)c1ccc(Cl)c([N+](=O)[O-])c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 89.4 %

Procedure:
100 g (0.5 mol) of 4-chloro-3-nitrobenzoic acid, 36 g (0.6 mol) of urea and 0.5 g of phosphorous acid are heated in 250 ml of 1,2-dichlorobenzene with stirring at from 165° to 178° C. for 8 h. After cooling to 25° C. the solid is filtered off with suction and washed with 50 ml of 1,2-dichlorobenzene. The filter cake is introduced into 250 ml of water, and the mixture is adjusted to a pH of 12 using aqueous sodium hydroxide solution and subjected to steam distillation. Subsequently the solid is filtered off with suction and dried at 100° C. 89.7 g of 4-chloro-3-nitrobenzamide are obtained having a melting point of from 146° to 149° C. This corresponds to a yield of 90.2% of theory. By acidification of the aqueous mother liquor to pH 2, 4.9 g of 4-chloro-3-nitrobenzoic acid (4.9% of theory) are obtained, which can be employed again in a subsequent batch.
Reaction SMILES: [CH3:1][N:2]1[C:6]([CH:7]([CH2:10][CH:11]=[CH2:12])[CH2:8][OH:9])=[C:5]([N+:13]([O-:15])=[O:14])[CH:4]=[N:3]1.[H-].[Na+].[CH2:18](Br)[CH:19]=[CH2:20]>CN(C=O)C>[CH2:20]([O:9][CH2:8][CH:7]([C:6]1[N:2]([CH3:1])[N:3]=[CH:4][C:5]=1[N+:13]([O-:15])=[O:14])[CH2:10][CH:11]=[CH2:12])[CH:19]=[CH2:18]
Reactant: C=CCBr
Reactant: C=CCC(CO)c1c([N+](=O)[O-])cnn1C
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: C=CCOCC(CC=C)c1c([N+](=O)[O-])cnn1C
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 77.6 %

Procedure:
To a solution of 2-(2-methyl-4-nitro-pyrazol-3-yl)pent-4-en-1-ol (91 mg, 0.43) in anhydrous DMF (5 mL) was added at 0° C. sodium hydride (20 mg, 0.49 mmol, 60 mass %). After stirring at 0° C. for 15 min, allyl bromide (79, 0.64 mmol) was added slowly, stirred at 0° C. for 10 min then warm to room temperature for 2 h. The reaction was quenched with water (10 ml) and extracted with EA (3×50 ml). Combined organic layer was washed with brine (10 ml) and concentrated to dryness. The residue was purified via silica gel chromatography (0-100% EtOAc/heptane) to afford 5-[1-(allyloxymethyl)but-3-enyl]-1-methyl-4-nitro-pyrazole (84 mg, 78%).
Reaction SMILES: [CH3:1][C:2](=O)[CH2:3][C:4](=[O:6])[CH3:5].[NH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[C:9]1([NH:8]/[C:2](/[CH3:1])=[CH:3]\[C:4](=[O:6])[CH3:5])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: Nc1ccccc1
Reactant: CC(=O)CC(C)=O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: Cc1ccccc1
Product: CC(=O)/C=C(/C)Nc1ccccc1

Procedure:
A solution of 2,4-pentanedione (7.2 ml), aniline (7.65 ml) and a catalytic amount of para-toluenesulfonic acid monohydrate (665 mg) in toluene (70 ml) was refluxed for 8 h in a round bottom flask equipped with a Dean Stark apparatus and condenser. The solution was concentrated to dryness and the crude purified by CC (Hept/EA 8:2, then 7:3) to give 6.74 g of the desired compound.
Reaction SMILES: [OH2:1].[OH-].[Li+].O.OO.C([C@@H]1COC(=O)N1C(=O)[C@H:21]([C@@H:33]1[CH2:37][CH2:36][CH2:35][N:34]1[C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[C:22]1[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[C:24]([F:32])[CH:23]=1)C1C=CC=CC=1.C1[CH2:50][O:49]CC1>>[C:41]([O:40][C:38]([N:34]1[CH2:35][CH2:36][CH2:37][C@H:33]1[C@H:21]([C:22]1[CH:27]=[CH:26][C:25]([C:28]([F:30])([F:29])[F:31])=[C:24]([F:32])[CH:23]=1)[C:50]([OH:49])=[O:1])=[O:39])([CH3:43])([CH3:42])[CH3:44]
Reactant: O
Reactant: C1CCOC1
Reactant: CC(C)(C)OC(=O)N1CCC[C@H]1[C@@H](C(=O)N1C(=O)OC[C@H]1Cc1ccccc1)c1ccc(C(F)(F)F)c(F)c1
Agent: OO
Agent: [Li+]
Agent: [OH-]
Product: CC(C)(C)OC(=O)N1CCC[C@H]1[C@@H](C(=O)O)c1ccc(C(F)(F)F)c(F)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 3.52 %

Procedure:
Lithium hydroxide hydrate (0.22 g, 5.24 mmol) was dissolved in THF (20 mL) and water (10 mL) and then treated with hydrogen peroxide (35 wt %) (1.00 g, 10.3 mmol). After stirring at ambient temperature for 30 minutes, the solution was cooled to 0° C. (S)-tert-Butyl 2-((S)-2-((R)-4-benzyl-2-oxooxazolidin-3-yl)-1-(3-fluoro-4-(trifluoromethyl)phenyl)-2-oxoethyl)pyrrolidine-1-carboxylate (1.44 g, 2.62 mmol) was added as a solution in THF (10 mL). The mixture was stirred at 0° C. for 1 hour and then warmed to ambient temperature overnight. The reaction was quenched with 10% K2SO3 (4 mL) and saturated NaHCO3 (4 mL) and stirred at ambient temperature for 20 minutes. The reaction was concentrated in vacuo, and the aqueous phase was washed with ether (3×50 mL). The aqueous phase was diluted with ethyl acetate (50 mL), cooled to 0° C., and acidified with 1N HCl to a pH of 3. The organic phase was separated, and the aqueous phase was extracted with ethyl acetate (3×50 mL). The combined organic phase was washed with 1N HCl (2×20 mL), dried over Na2SO4 and then concentrated in vacuo (0.036 g, 3.52% yield). MS (APCI−) [M−H] 389.8.
Reaction SMILES: Br[C:2]1[CH:11]=[CH:10][C:5]2[N:6]=[C:7](C)[O:8][C:4]=2[CH:3]=1.C[N:13]([CH:15]=O)C.[N-:17]=[N+:18]=[N-].[Na+]>O>[N:13]([CH2:15][C:2]1[CH:11]=[CH:10][C:5]2[N:6]=[CH:7][O:8][C:4]=2[CH:3]=1)=[N+:17]=[N-:18]
Reactant: Cc1nc2ccc(Br)cc2o1
Reactant: [N-]=[N+]=[N-]
Reactant: CN(C)C=O
Agent: [Na+]
Solvent: O
Product: [N-]=[N+]=NCc1ccc2ncoc2c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A 100 ml flask was loaded with 6-bromo-methyl-benzooxazole (1.8 g, 8.5 mmole), 40 ml DMF and sodium azide (1.1 g, 16.98 mmole). The reaction mixture was stirred at room temperature, overnight. The reaction mixture was diluted with 40 ml water and extracted 2×50 ml EtOAc. Combined organic layers were washed with water, brine, dried over sodium sulfate, filtered and concentrated to afford 2 g oily crude. HNMR shows 90% pure product. This was used for next step.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[CH:14]=[CH:13][C:12]([N+:15]([O-])=O)=[CH:11][N:10]=2)=[CH:4][C:3]=1[NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22].O1CCCC1>CO.[C].[Pd]>[NH2:15][C:12]1[CH:13]=[CH:14][C:9]([O:8][C:5]2[CH:6]=[CH:7][C:2]([F:1])=[C:3]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:22])([CH3:23])[CH3:24])[CH:4]=2)=[N:10][CH:11]=1
Reactant: CC(C)(C)OC(=O)Nc1cc(Oc2ccc([N+](=O)[O-])cn2)ccc1F
Agent: [Pd]
Solvent: CO
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)Nc1cc(Oc2ccc(N)cn2)ccc1F
Temperature: 25 °C
Reaction time: 8 h
Yield: 93.9 %

Procedure:
A suspension of tert-butyl {2-fluoro-5-[(5-nitropyridin-2-yl)oxy]phenyl}carbamate (3.49 g, 10 mmol) and 10% palladium-carbon (1.0 g) in methanol (20 mL)-tetrahydrofuran (20 mL) was vigorously stirred at room temperature overnight under a hydrogen atmosphere. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The to residue was poured into water (200 mL), and the mixture was extracted with ethyl acetate (100 mL×2). The ethyl acetate layers were combined and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The residue was triturated with diethyl ether to give the title compound (3.00 g, 94%) as a colorless powder.
Reaction SMILES: [O:1]([CH2:19][CH:20]([CH3:51])[CH2:21][CH2:22][CH2:23][C:24]([CH3:50])([O:46][CH2:47][S:48][CH3:49])[C:25](=[O:45])[CH2:26][CH2:27][C:28]1([O:44][CH2:43][CH2:42][O:41]1)[CH2:29][O:30][S:31]([C:34]1[CH:40]=[CH:39][C:37]([CH3:38])=[CH:36][CH:35]=1)(=[O:33])=[O:32])[Si:2]([C:15]([CH3:18])([CH3:17])[CH3:16])([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[BH4-].[Na+]>CO>[O:1]([CH2:19][CH:20]([CH3:51])[CH2:21][CH2:22][CH2:23][C:24]([CH3:50])([O:46][CH2:47][S:48][CH3:49])[CH:25]([OH:45])[CH2:26][CH2:27][C:28]1([O:44][CH2:43][CH2:42][O:41]1)[CH2:29][O:30][S:31]([C:34]1[CH:35]=[CH:36][C:37]([CH3:38])=[CH:39][CH:40]=1)(=[O:32])=[O:33])[Si:2]([C:15]([CH3:18])([CH3:17])[CH3:16])([C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: CSCOC(C)(CCCC(C)CO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C)C(=O)CCC1(COS(=O)(=O)c2ccc(C)cc2)OCCO1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: CSCOC(C)(CCCC(C)CO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C)C(O)CCC1(COS(=O)(=O)c2ccc(C)cc2)OCCO1
Reaction time: 2 h
Yield: 97.3 %

Procedure:
11-t-Butyldiphenylsiloxy-6,10-dimethyl-2,2-ethylenedioxy-6-methylthiomethoxy-5-oxo-1-tosyloxyundecane (0.493 g) in methanol (30 ml) is cooled to 0° C.; sodium borohydride (0.438 g) is added and the resulting solution is stirred for 2 hours. The solvent is removed in vacuo and the residue is neutralized to pH 7 with aqueous hydrochloric acid and extracted with ether. The ether extract is washed with brine and dried over sodium sulfate. The solvent is removed in vacuo to give 11-t-butyldiphenylsiloxy-6,10-dimethyl-2,2-ethylenedioxy-5-hydroxy-6-methylthiomethoxy-1-tosyloxyundecane (0.481 g) as an epimeric mixture of alcohols. The alcohols are separated by chromatography on silica employing ethyl acetate:hexane as the eluting solvent. The epimers have the following nmr spectra: