Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [BH4-].[Li+].C([O:5][C:6](=O)[CH:7]([NH2:17])[CH:8]([C:13]([F:16])([F:15])[F:14])[C:9]([F:12])([F:11])[F:10])C.Cl>C1COCC1>[F:10][C:9]([F:11])([F:12])[CH:8]([C:13]([F:14])([F:15])[F:16])[CH:7]([NH2:17])[CH2:6][OH:5]
Reactant: CCOC(=O)C(N)C(C(F)(F)F)C(F)(F)F
Agent: Cl
Agent: [BH4-]
Agent: [Li+]
Solvent: C1CCOC1
Product: NC(CO)C(C(F)(F)F)C(F)(F)F
Yield: 76.6 %

Procedure:
A solution of lithium borohydride (2M THF, 19.8 mL) was added to a solution of 2-amino-4,4,4-trifluoro-3-trifluoromethyl-butyric acid ethyl ester (5 g, 19.8 mmol), prepared as described (J. Med Chem. 1981, 24, 1043–1047), in THF (80 mL) at 25° C. and was stirred for 4 h. 2M HCl was added to the reaction mixture very carefully until a pH less than 2. The organic solvent was removed in vacuo and the aqueous layer was neutralized with sat NaHCO3 until pH=7. The aqueous layer was extracted with EtOAc (2×50 mL) and the organic extracts were dried over Na2SO4 and concentrated to provide 3,3,3-trifluoro-2-(trifluoromethyl)-1-(hydroxymethyl)propylamine as a yellow oil (3.2 g, 77% yield). The crude oil was of sufficient purity to utilize in the subsequent reaction.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH2:48][C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][C:50]=2[OH:55])[C:5]([OH:47])=[C:6]([CH:46]=1)[CH2:7][C:8]1[C:9]([OH:45])=[C:10]([CH:42]=[CH:43][CH:44]=1)[C:11]([O:13][CH2:14][C:15]1[CH2:16][S:17][C@@H:18]2[CH:29]([NH:30][C:31](=[O:40])[CH2:32][O:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[C:28](=[O:41])[N:19]2[C:20]=1[C:21]([O:23]C(C)(C)C)=[O:22])=[O:12]>C(C(O)=O)(F)(F)F.C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:48][C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][C:50]=2[OH:55])[C:5]([OH:47])=[C:6]([CH:46]=1)[CH2:7][C:8]1[C:9]([OH:45])=[C:10]([CH:42]=[CH:43][CH:44]=1)[C:11]([O:13][CH2:14][C:15]1[CH2:16][S:17][C@@H:18]2[CH:29]([NH:30][C:31](=[O:40])[CH2:32][O:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[C:28](=[O:41])[N:19]2[C:20]=1[C:21]([OH:23])=[O:22])=[O:12]
Reactant: CC(C)(C)OC(=O)C1=C(COC(=O)c2cccc(Cc3cc(Cl)cc(Cc4ccccc4O)c3O)c2O)CS[C@@H]2C(NC(=O)COc3ccccc3)C(=O)N12
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: O=C(COc1ccccc1)NC1C(=O)N2C(C(=O)O)=C(COC(=O)c3cccc(Cc4cc(Cl)cc(Cc5ccccc5O)c4O)c3O)CS[C@H]12
Yield: 90 %

Procedure:
A solution of 17 (3.93 g, 4.99 mmol) in CF3CO2H (35%) in CH2Cl2 (45 mL) was stirred at room temperature for 13 h. The solution was condensed under reduced pressure and then CCL4 (30 mL) was added to the residue and evaporated. The resultant solid was crystallized from a mixture of EtOH and ether (2:1) to afford pure 19 (3.28 g, 4.49 mmol) as a white crystal in 90% yield: mp 196-198° C.; 1H NMR (DMSO-d6/D2O) d 3.60 (br s, 4 H, 2×CH2), 3.68, 3.79 (AB, Jgem=19 Hz, 2 H, CH2S), 4.65 (s, 2 H, OCH2CO), 4.95 5.25 (AB, Jgem=14 Hz, 2 H, CH2O), 5.15 (d, J=5.1 Hz, 1 H, HC(6)), 5.76 (d, J=5.1 Hz, 1 H, HC(7)), 6.80-7.35 (m, 14 H, 4×ArH); IR (nujol): 3300-3450 (OH, NH, CO2H), 1785 (β-lactam), 1720 (ester), 1685 (amide), 1610 (C═O) cm−1. Anal. (C37H31N2O10SCl) C, H, N, S, Cl.
Reaction SMILES: [C:1]1(=[O:11])[NH:5][C:4](=[O:6])[C:3]2=[CH:7][CH:8]=[CH:9][CH:10]=[C:2]12.[K].[CH2:13]([CH:15]1[O:17][CH2:16]1)Br.O>CN(C=O)C>[O:17]1[CH2:16][CH:15]1[CH2:13][N:5]1[C:1](=[O:11])[C:2]2=[CH:10][CH:9]=[CH:8][CH:7]=[C:3]2[C:4]1=[O:6]
Reactant: O=C1NC(=O)c2ccccc21
Reactant: BrCC1CO1
Agent: [K]
Solvent: O
Solvent: CN(C)C=O
Product: O=C1c2ccccc2C(=O)N1CC1CO1
Temperature: 120 °C
Reaction time: 3 h
Yield: 51.2 %

Procedure:
Step1: To a suspension of potassium phthalimide (5.0 g, 27 mmol) in DMF (75 ml) was added epibromohydrin (2.5 ml, 29 mmol), and the mixture was stirred at 120° C. for 3 h. After adding water, the mixture was extracted with (hexane/ethyl acetate=3/1), washed with brine, dried over magnesium sulfate, and then filtered. Concentrating under vacuum gave N-(2,3-epoxypropyl)phthalimide (2.81 g, 51%) which was used in the next step without further purification.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[C:11]1[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]2[N:21]=[C:22]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[O:23][C:24]=2[C:25]([F:28])([F:27])[F:26])=[O:19])=[CH:13][N:12]=1)[C:5]([OH:7])=O.[CH3:35][S:36]([NH2:39])(=[O:38])=[O:37].Cl.C(N=C=NCCCN(C)C)C>CN(C)C1C=CN=CC=1.ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]([C:5]([NH:39][S:36]([CH3:35])(=[O:38])=[O:37])=[O:7])[CH:8]=[CH:9][C:10]=1[C:11]1[N:12]=[CH:13][C:14]([NH:17][C:18]([C:20]2[N:21]=[C:22]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[O:23][C:24]=2[C:25]([F:27])([F:28])[F:26])=[O:19])=[CH:15][CH:16]=1
Reactant: CS(N)(=O)=O
Reactant: O=C(O)c1ccc(-c2ccc(NC(=O)c3nc(-c4ccccc4)oc3C(F)(F)F)cn2)c(Cl)c1
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: ClCCl
Product: CS(=O)(=O)NC(=O)c1ccc(-c2ccc(NC(=O)c3nc(-c4ccccc4)oc3C(F)(F)F)cn2)c(Cl)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 35.4 %

Procedure:
According to the procedures described in Tetrahedron Lett. 1998, 39, 5891 and Org. Proc. Res. Dev. 2004, 8, 952, 3-chloro-4-{5-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-pyridin-2-yl}-benzoic acid (30 mg, 0.06 mmol), methanesulfonamide (7 mg, 0.07 mmol), 4-dimethylaminopyridine (2 mg, 0.02 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (14 mg, 0.07 mmol) were suspended in 3 mL of dichloromethane and the mixture was refluxed for 3 h. The reaction mixture was cooled down to room temperature and filtered. The white precipitates were washed with ethyl acetate. The combined filtrate was stirred with 150 mg of Amberlyst-15 at room temperature for 2 h. The reaction was filtered to remove the resin, and the filtrate was concentrated and purified by flash chromatography (eluting with ethyl acetate and hexanes) to afford 12 mg of 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid [6-(2-chloro-4-methanesulfonylaminocarbonyl-phenyl)-pyridin-3-yl]-amide as a light yellow solid. LCMS calcd for C24H16ClF3N4O5S (m/e) 564, obsd 565 (M+H).
Reaction SMILES: [Br:1][C:2]1[N:6]=[C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([O:13][C:14]([F:17])([F:16])[F:15])[CH:8]=2)[N:4]([CH3:18])[C:3]=1[CH2:19][OH:20]>CCOC(C)=O.[O-2].[Mn+4].[O-2]>[Br:1][C:2]1[N:6]=[C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([O:13][C:14]([F:17])([F:16])[F:15])[CH:8]=2)[N:4]([CH3:18])[C:3]=1[CH:19]=[O:20]
Reactant: Cn1c(-c2cccc(OC(F)(F)F)c2)nc(Br)c1CO
Agent: [Mn+4]
Agent: [O-2]
Solvent: CCOC(C)=O
Product: Cn1c(-c2cccc(OC(F)(F)F)c2)nc(Br)c1C=O
Temperature: 50 °C
Reaction time: 5 h

Procedure:
A solution of 2.80 g (8.0 mmol) of [5-bromo-3-methyl-2-(3-trifluoromethoxy-phenyl)-3H-imidazol-4-yl]-methanol in 120 ml of EtOAc was treated in small portions with 4.85 g (55.8 mmol) of manganese(IV) oxide; the reaction mixture was stirred at RT for 2 hours and at 50° C. for 5 hours, it was then cooled down to RT and filtered (with the aid of dicalite) and the solvents were evaporated to give 2.813 g (quant.) of the title compound as colorless oil. MS: 349.0 (MH+, 1Br).
Reaction SMILES: [C:1]([O:5][C:6](=[O:24])[NH:7][C@@:8]12[CH2:23][O:22][CH2:21][CH:9]1[CH2:10][N:11]([C@@H](C1C=CC=CC=1)C)[CH2:12]2)([CH3:4])([CH3:3])[CH3:2]>O1CCOCC1.[OH-].[Pd+2].[OH-]>[C:1]([O:5][C:6](=[O:24])[NH:7][C@@:8]12[CH2:23][O:22][CH2:21][CH:9]1[CH2:10][NH:11][CH2:12]2)([CH3:4])([CH3:2])[CH3:3]
Reactant: C[C@H](c1ccccc1)N1CC2COC[C@@]2(NC(=O)OC(C)(C)C)C1
Agent: [Pd+2]
Agent: [OH-]
Solvent: C1COCCO1
Product: CC(C)(C)OC(=O)N[C@]12CNCC1COC2
Temperature: 40 °C
Reaction time: 24 h
Yield: 100.4 %

Procedure:
[(3aS)-5-[(R)-1-Phenylethyl]tetrahydrofuro[3,4-c]pyrrol-3a-yl]carbamic acid tert-butyl ester (355 mg, 1.06 mmol) was dissolved in dioxane (10 ml) and 20% palladium hydroxide catalyst (20 wt. % Pd on carbon, wet; cat.) was added. The mixture was vigorously stirred under a hydrogen atmosphere at 40° C. for 24 h. After removing the catalyst by filtration, the filtrate was concentrated under reduced pressure. The residue was taken up in dichloromethane, and washed with 1N aq. NaOH and brine. The organic layer was dried over anhydrous sodium sulfate and the solvent removed in vacuo to give the crude title compound (243 mg) as a colorless syrup.
Reaction SMILES: [Br:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[Cl:11])[NH:4][N:3]=1.[O:12]1[C:16]2([CH2:21][CH2:20][CH:19](O)[CH2:18][CH2:17]2)[O:15][CH2:14][CH2:13]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[Br:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[Cl:11])[N:4]([CH:19]2[CH2:20][CH2:21][C:16]3([O:15][CH2:14][CH2:13][O:12]3)[CH2:17][CH2:18]2)[N:3]=1
Reactant: OC1CCC2(CC1)OCCO2
Reactant: Clc1ncnc2[nH]nc(Br)c12
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: Clc1ncnc2c1c(Br)nn2C1CCC2(CC1)OCCO2
Temperature: 0 °C
Reaction time: 1 h
Yield: 68.6 %

Procedure:
To a solution of 3-bromo-4-chloropyrazolo[3,4-d]pyrimidine (Intermediate B) (7.5 g, 32 mmol), 1,4-dioxaspiro[4.5]decan-8-ol (Intermediate M) (15.17 g, 96 mmol), triphenylphosphine (16.86 g, 64 mmol) in THF (275 mL) was added diethylazodicarboxylate (11.14 g, 64 mmol) in THF (50 mL) at 0° C. under nitrogen. The reaction mixture was stirred at 0° C. for 1 hour, warmed to room temperature and then stirred at room temperature for 3 hrs. The reaction mixtures was concentrated in vacuo and dissolved in hot heptane/EtOAc/DCM (5:1:5). Flash silica gel column chromatography using heptane, heptane/EtOAc (5/1) then heptane/EtOAc (4/1) gave a solid which was triturated with heptane and the solids removed by filtration to furnish 8.2 g of 3-bromo-4-chloro-1-(1,4-dioxaspiro[4.5]dec-8-yl)-1H-pyrazolo[3,4-d]pyrimidine as a white solid (69%) [Rf in 1:1 heptane:EtOAc=0.5]1H NMR (400 MHz, d6-DMSO): 8.89 (1H, s), 4.92 (1H, m), 3.90 (4H, m), 2.16 (2H, m), 1.96 (2H, m), 1.81 (6H, m) HPLC: Tr=17.11 mins, 96.6%
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][CH:3]=1.[N:12]([C:15]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[N:18]=[C:17]([C:25]([F:28])([F:27])[F:26])[CH:16]=1)=[C:13]=[S:14]>C1C=CC=CC=1.C(N(CC)CC)C>[F:27][C:25]([F:26])([F:28])[C:17]1[CH:16]=[C:15]([NH:12][C:13]([NH:1][C:2]2[CH:7]=[CH:6][C:5]([C:8]([F:9])([F:10])[F:11])=[CH:4][CH:3]=2)=[S:14])[CH:20]=[C:19]([C:21]([F:24])([F:22])[F:23])[N:18]=1
Reactant: FC(F)(F)c1cc(N=C=S)cc(C(F)(F)F)n1
Reactant: Nc1ccc(C(F)(F)F)cc1
Solvent: c1ccccc1
Solvent: CCN(CC)CC
Product: FC(F)(F)c1ccc(NC(=S)Nc2cc(C(F)(F)F)nc(C(F)(F)F)c2)cc1
Yield: 72.9 %

Procedure:
A mixture of 4-aminobenzotrifluoride (1.48 g) and 4-isothiocyanato-2,6-bis(trifluoromethyl)pyridine (2.5 g, 0.01 mole) in dry benzene (25 ml) containing several drops of triethylamine was heated under reflux for 7 hours. Removal of the solvent and triethylamine gave the title compound as a colorless solid 2.9 g, m.p. 125°-132° C. Crystallization from benzene furnished a sample, m.p. 132° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([NH:14][C:15](=[O:26])[C:16]#[C:17][C:18]3[CH:23]=[CH:22][C:21]([CH2:24][OH:25])=[CH:20][CH:19]=3)=[CH:10][CH:9]=2)=[C:4]([F:27])[CH:3]=1.[CH3:28][S:29](Cl)(=[O:31])=[O:30].ClCCl.CO.N>>[CH3:28][S:29]([O:25][CH2:24][C:21]1[CH:22]=[CH:23][C:18]([C:17]#[C:16][C:15](=[O:26])[NH:14][C:11]2[CH:12]=[CH:13][C:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][C:4]=3[F:27])=[CH:9][CH:10]=2)=[CH:19][CH:20]=1)(=[O:31])=[O:30]
Reactant: CS(=O)(=O)Cl
Reactant: O=C(C#Cc1ccc(CO)cc1)Nc1ccc(-c2ccc(Cl)cc2F)cc1
Agent: N
Solvent: ClCCl
Solvent: CO
Product: CS(=O)(=O)OCc1ccc(C#CC(=O)Nc2ccc(-c3ccc(Cl)cc3F)cc2)cc1

Procedure:
Prepared analogously to Example 1.2.b. from 3-(4-hydroxymethylphenyl)propynoic acid-(4′-chloro-2′-fluorobiphenyl-4-yl)amide and methanesulfonic acid chloride. Yield: 0.23 g (50% of theory); C23H17ClFN2O2S (M=457.91); calc.: molecular ion peak (M+H)+: 456/458; found: molecular ion peak (M+H)+: 456/458; Rf value: 0.5 (silica gel, dichloromethane/methanol/ammonia (20:1:0.1)).
Reaction SMILES: [CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[CH2:3][C:2]21[CH2:16][CH2:15][C:14](=[O:17])[CH2:13][CH2:12]2.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1C=CC=CC=1>[CH2:1]1[C:10]2[CH:5]([CH2:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[CH2:3][C:2]21[CH2:16][CH2:15][C:14](=[O:17])[CH2:13][CH2:12]2
Reactant: O=C1CCC2(CC1)CC(=O)c1ccccc1C2
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: c1ccccc1
Product: O=C1CCC2(CC1)CC(=O)C1CC=CC=C1C2

Procedure:
A 3', 4'-dihydrospiro[cyclohexane-1,2'(1'H)-naphthalene]-4', 4-dione (6) obtained in step (6) is monoketalized at the non-conjugated least hindered carbonyl function, e.g., by heating (at reflux) in a solvent such as benzene with an alkylene glycol (in the presence of a catalyst such as p-toluenesulfonic acid), to yield a corresponding 3', 4', -dihydrospiro[cyclohexane-1,2'(1'H)-naphthalene]-4',4 -dione, 4-(ethylene ketal) (7).
Reaction SMILES: [NH:1](C(OC(C)(C)C)=O)[C@H:2]([C:4]([NH:6][C@H:7]([C:11]([NH:13][C@H:14]([C:30]([NH2:32])=[O:31])[CH2:15][CH2:16][CH2:17][CH2:18][NH:19][C:20]([O:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[O:21])=[O:12])[CH:8]([CH3:10])[CH3:9])=[O:5])[CH3:3].[C:40]([OH:46])([C:42]([F:45])([F:44])[F:43])=[O:41]>>[NH2:1][C@H:2]([C:4]([NH:6][C@H:7]([C:11]([NH:13][C@H:14]([C:30]([NH2:32])=[O:31])[CH2:15][CH2:16][CH2:17][CH2:18][NH:19][C:20]([O:22][CH2:23][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)=[O:21])=[O:12])[CH:8]([CH3:10])[CH3:9])=[O:5])[CH3:3].[F:43][C:42]([C:40]([OH:46])=[O:41])([F:45])[F:44]
Reactant: CC(C)[C@H](NC(=O)[C@H](C)NC(=O)OC(C)(C)C)C(=O)N[C@@H](CCCCNC(=O)OCc1ccccc1)C(N)=O
Solvent: O=C(O)C(F)(F)F
Product: CC(C)[C@H](NC(=O)[C@H](C)N)C(=O)N[C@@H](CCCCNC(=O)OCc1ccccc1)C(N)=O
Reaction time: 0.17 h
Yield: 83 %

Procedure:
The protected tripeptide amide (IX) (1.0 g, 1.8 mmol) was dissolved in cold TFA (10 ml). After 10 minutes, the mixture was evaporated in vacuo and the residue was triturated with ether (2×50 ml). The mother liquors were decanted and the residue was dried under vacuum to give (X) as a foam (0.85 g; 83%).
Reaction SMILES: C([O:3][C:4]([C:6]1[C:7]2[CH2:8][C@H:9]3[CH2:21][C@H:10]3[C:11]=2[N:12]([C:14]2[CH:19]=[C:18]([Br:20])[CH:17]=[CH:16][N:15]=2)[N:13]=1)=[O:5])C.[OH-].[Na+]>C1COCC1.CO>[Br:20][C:18]1[CH:17]=[CH:16][N:15]=[C:14]([N:12]2[C:11]3[C@@H:10]4[CH2:21][C@@H:9]4[CH2:8][C:7]=3[C:6]([C:4]([OH:5])=[O:3])=[N:13]2)[CH:19]=1
Reactant: CCOC(=O)c1nn(-c2cc(Br)ccn2)c2c1C[C@H]1C[C@@H]21
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: O=C(O)c1nn(-c2cc(Br)ccn2)c2c1C[C@H]1C[C@@H]21
Temperature: 23 °C
Reaction time: 2 h
Yield: 100.5 %

Procedure:
To a solution of (1aR,5aR)-2-(4-bromo-pyridin-2-yl)-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid ethyl ester (9.0 g, 25.8 mmol) in THF (50 mL) and MeOH (50.0 mL) was added a 2.0 M aqueous solution of sodium hydroxide (25.8 mL, 51.7 mmol). The reaction was stirred at 23° C. for 2 h then concentrated to remove the organic solvents. The remaining residue was diluted to 150 mL with water. This solution was filtered to remove trace insoluble impurities then acidified to pH ˜3 with 6 M HCl. The resulting precipitate was collected by filtration, rinsed with water, then dried under vacuum to give the title compound (8.3 g) as a white solid. LCMS m/z=320.0 [M+H]+.
Reaction SMILES: Br[C:2](Cl)(Cl)[C:3]([Br:6])(Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F:28][C:29]([F:44])([F:43])[C:30]1[CH:31]=[C:32]([C@@H](O)C)[CH:33]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:35]=1.CCCCCC>C1(C)C=CC=CC=1>[Br:6][C@@H:3]([C:32]1[CH:33]=[C:34]([C:36]([F:39])([F:37])[F:38])[CH:35]=[C:30]([C:29]([F:28])([F:44])[F:43])[CH:31]=1)[CH3:2]
Reactant: ClC(Cl)(Br)C(Cl)(Cl)Br
Reactant: C[C@H](O)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Solvent: CCCCCC
Product: C[C@@H](Br)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 88.6 %

Procedure:
Under an argon atmosphere, 1,2-dibromo-1,1,2,2-tetrachloroethane (7.57 g, 23.2 mmol) was dissolved in toluene (12.5 mL), the solution was added with triphenylphosphine (6.1 g, 23.2 mmol) at 0° C., and the mixture was stirred for 30 minutes. The reaction mixture was added dropwise with a solution of (S)-1-[3,5-bis(trifluoromethyl)phenyl]ethanol (5.0 g, 19.4 mmol, >99.5% ee) in toluene (12.5 mL) at 0° C. over 10 minutes or more, and then the mixture was warmed to room temperature, and stirred at the same temperature for 1 hour. The reaction mixture was added with n-hexane (25 mL), and the mixture was filtered through Celite. The filtrate was washed successively with water, saturated aqueous sodium hydrogencarbonate, and saturated brine, dried over sodium sulfate, and evaporated under reduced pressure. The resulting residue was distilled under reduced pressure (56° C., 0.7 mmHg) to obtain 5.52 g of (R)-1-bromo-1-[3,5-bis(trifluoromethyl)phenyl]ethane as colorless oil.
Reaction SMILES: [CH:1]1[C:13]2[N:12]([CH2:14][CH2:15][CH2:16][P:17](=[O:24])([O:21][CH2:22][CH3:23])[O:18][CH2:19][CH3:20])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.[Cl-].[Al+3].[Cl-].[Cl-].Cl[C:30]([CH3:33])([CH3:32])[CH3:31]>>[C:30]([C:8]1[CH:9]=[CH:10][C:11]2[N:12]([CH2:14][CH2:15][CH2:16][P:17](=[O:24])([O:21][CH2:22][CH3:23])[O:18][CH2:19][CH3:20])[C:13]3[C:5]([C:6]=2[CH:7]=1)=[CH:4][C:3]([C:5]([CH3:6])([CH3:13])[CH3:4])=[CH:2][CH:1]=3)([CH3:33])([CH3:32])[CH3:31]
Reactant: CCOP(=O)(CCCn1c2ccccc2c2ccccc21)OCC
Reactant: CC(C)(C)Cl
Agent: [Al+3]
Agent: [Cl-]
Product: CCOP(=O)(CCCn1c2ccc(C(C)(C)C)cc2c2cc(C(C)(C)C)ccc21)OCC
Reaction time: 0.42 h

Procedure:
Diethyl 3-(9H-carbazol-9-yl)propylphosphonate (1.00 g, 2.89 mmol) was dissolved in 2-chloro-2-methylpropane (5.0 mL) and flushed with N2 for 5 minutes. To this stirred solution was added aluminum chloride (1.16 g, 8.67 mmol) slowly. The solution turned chunky and black with gas bubbles appearing. The reaction was allowed to stir for 25 minutes after adding all the aluminum chloride. It was then quenched with 25 mL water and an extraction performed with water washings followed by 2×20 mL 1 M NaOH washings, then another water washing. The yellow organic layer was kept and dried and the solvent removed under vacuum. A tlc in ethyl acetate showed 4 spots with the brightest (and desired product) being the third spot from the top. A long column was run and the desired product was obtained as a thick yellow oil (447 mg, 34% yield). 1H NMR (400.14 MHz, CD2Cl2) δ 8.10 (d, J=1.6 Hz, 2H), 7.52 (dd, J=8.80, 2.00 Hz, 2H), 7.35 (d, 8.40 Hz, 2H), 4.36 (t, J=7.00 Hz, 2H), 4.08-3.93 (m, 4H), 2.21-2.07 (m, 2H), 1.71 (dt, J=18.14 Hz, 6.00 Hz, 2H), 1.45 (18H), 1.25 (t, J=7.00 Hz, 6H). 13C{1H} NMR (100.61 MHz, CD2Cl2) δ 142.14 (2C), 139.26 (2C), 123.80 (2C), 123.06 (2C), 116.68 (2C), 108.50 (2C), 61.89 (d, J=6.4 Hz, 2C), 43.36 (d, J=15.8 Hz), 34.92 (2C), 32.19 (6C), 23.35 (d, 142.2 Hz), 22.59 (d, J=4.9 Hz), 16.64 (d, J=5.8 Hz, 2C). 31P{1H} NMR (161.97 MHz, CD2Cl2): δ 31.34.
Reaction SMILES: [CH2:1]([O:9][CH2:10][CH2:11][OH:12])[CH:2]=[CH:3][CH2:4][CH2:5][CH2:6][CH:7]=[CH2:8].[C:13](OC)(=[O:17])[C:14]([CH3:16])=[CH2:15]>>[CH3:16][C:14](=[CH2:15])[C:13]([O:12][CH2:11][CH2:10][O:9][CH2:1]/[CH:2]=[CH:3]/[CH2:4][CH2:5][CH2:6][CH:7]=[CH2:8])=[O:17]
Reactant: C=CCCCC=CCOCCO
Reactant: C=C(C)C(=O)OC
Product: C=CCCC/C=C/COCCOC(=O)C(=C)C

Procedure:
The resulting 2-octa-2,7-dienyloxyethanol was subsequently reacted with methyl methacrylate to give 2-((2-E)octa-2,7-dienyloxy)ethyl 2-methylprop-2-enoate.
Reaction SMILES: [CH3:1]/[C:2](=[CH:6]\[C:7]1[CH:12]=[CH:11][C:10]([CH2:13][C:14]2[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=2)=[CH:9][CH:8]=1)/[C:3]([OH:5])=[O:4].[OH-].C[N+](C)(C)C>CO>[CH2:1]([O:4][C:3](=[O:5])/[C:2](/[CH3:1])=[CH:6]/[C:7]1[CH:12]=[CH:11][C:10]([CH2:13][C:14]2[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=2)=[CH:9][CH:8]=1)[CH2:2][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:13][CH2:14][CH3:19]
Reactant: C/C(=C\c1ccc(Cc2cccnc2)cc1)C(=O)O
Agent: C[N+](C)(C)C
Agent: [OH-]
Solvent: CO
Product: CCCCCCCCCCOC(=O)/C(C)=C/c1ccc(Cc2cccnc2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 53.9 %

Procedure:
A solution of 126.5 mg of the acrylic acid(prepared as described in Example 15) in 3 ml of methanol was stirred with 0.1 ml of a 10% W/W solution of tetramethylammonium hydroxide in methanol at room temperature for 20 minutes, and the mixture was concentrated under reduced pressure. The residue was dissolved in 3 ml of N,N-dimethylformamide, the solution was stirred overnight with 0.1033 ml of decyl bromide at room temperature, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel using a 1% V/V solution of ethanol in chloroform as eluent to give 53 mg of the title compound having the following physical characteristics:
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:11]([OH:13])[CH3:12])[CH:5]=[C:6]([N+:8]([O-:10])=[O:9])[CH:7]=1>O1CCOCC1>[Br:1][C:2]1[CH:3]=[C:4]([C:11](=[O:13])[CH3:12])[CH:5]=[C:6]([N+:8]([O-:10])=[O:9])[CH:7]=1
Reactant: CC(O)c1cc(Br)cc([N+](=O)[O-])c1
Solvent: C1COCCO1
Product: CC(=O)c1cc(Br)cc([N+](=O)[O-])c1

Procedure:
1-(3-Bromo-5-nitro-phenyl)-ethanol (12.84 g, 52.2 mmol) was dissolved in dioxane (245 ml) and manganedioxide (31.8 g, 365 mmol) was added. The reaction was refluxed for 17 hrs. The reaction was filtered and solvent was removed under reduced pressure yielding the title compound as yellow solid. 1H-NMR (500 MHz, DMSO-d6): 8.64 (s, 1H), 8.58 (s, 1H), 8.53 (s, 1H), 2.70 (s, 3H); GC/MS: 243 [(M)+].
Reaction SMILES: [CH3:1][C:2]([CH3:10])([C:4](=[O:9])[CH2:5][C:6](=O)[CH3:7])[CH3:3].S([O-])([O-])(=O)=O.[Na+].[Na+].[CH:18]([NH2:22])([CH2:20][CH3:21])[CH3:19]>C1(C)C=CC=CC=1>[CH3:1][C:2]([CH3:10])([C:4](=[O:9])[CH2:5][CH:6]([NH:22][CH:18]([CH2:20][CH3:21])[CH3:19])[CH3:7])[CH3:3]
Reactant: CC(=O)CC(=O)C(C)(C)C
Reactant: CCC(C)N
Agent: O=S(=O)([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: CCC(C)NC(C)CC(=O)C(C)(C)C
Yield: 69.9 %

Procedure:
To a solution of 5.00 g (35.16 mmol) 2,2-dimethyl-3,5-hexanedione in 20 mL of toluene loaded with 10.00 g of sodium sulfate was added 5.14 g (70.32 mmol) sec-butylamine. The mixture was refluxed 3 days. 4.90 g of light yellow oil was obtained after work-up. The isolated yield was 71%. 1H NMR (500 MHz, C6D6): δ=11.52 (s, 1H), 5.18 (s, 1H), 2.95 (m, 1H), 1.51 (s, 3H), 1.31 (s, 9H), 1.14 (s, 2H), 0.80 (d, 3H), 0.67 (t, 3H).
Reaction SMILES: OC1[CH:7]=[CH:6][C:5]([C:8]([C:11]2[CH:16]=[CH:15][C:14]([OH:17])=[C:13]([Cl:18])[CH:12]=2)([CH3:10])[CH3:9])=CC=1Cl.[CH3:20]C(=C)C>C1(C)C=CC=CC=1>[OH:17][C:14]1[CH:15]=[C:16]2[C:11](=[CH:12][C:13]=1[Cl:18])[C:8]([CH3:9])([CH3:10])[CH2:5][C:6]2([CH3:7])[CH3:20]
Reactant: CC(C)(c1ccc(O)c(Cl)c1)c1ccc(O)c(Cl)c1
Reactant: C=C(C)C
Solvent: Cc1ccccc1
Product: CC1(C)CC(C)(C)c2cc(Cl)c(O)cc21
Temperature: 230 °C
Reaction time: 6 h
Yield: 16.7 %

Procedure:
99 g (0.33 mol) of 2,2-bis-(4-hydroxy-3-chlorphenyl)-propane, 20 g of an acid-activated fuller's earth and 60 g (1.07 mol) of isobutylene are introduced into an autoclave. After stirring for 6 hours at 230° C., 200 ml of toluene are added, the catalyst is filtered off and the solvent evaporated. The residue (127.1 g) is distilled in vacuo in a packed column. 12.2 g (0.055 mol) of 5-hydroxy-6-chlor-1,1,3,3-tetramethyl indane (VII) melting at 51° C. are obtained from the fraction boiling at 75°-83° C./0.2 Torr by recrystallisation from 25 ml of petroleum ether. ##STR25##