Water → 2-[(4-Chloro-phenylsulfanyl)-(2,3,6-trifluoro-phenyl)-methyl]-propane-1,3-diol

HRID 1047491Notes

Reaction equation

HRID 1047491 reaction equation
C[O:2][C:3](=O)[CH:4]([CH:9]([S:19][C:20]1[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=1)[C:10]1[C:15]([F:16])=[CH:14][CH:13]=[C:12]([F:17])[C:11]=1[F:18])[C:5](OC)=[O:6].CC(C[AlH]CC(C)C)C.O.C(OCC)(=O)C>C1COCC1>[Cl:26][C:23]1[CH:24]=[CH:25][C:20]([S:19][CH:9]([C:10]2[C:15]([F:16])=[CH:14][CH:13]=[C:12]([F:17])[C:11]=2[F:18])[CH:4]([CH2:5][OH:6])[CH2:3][OH:2])=[CH:21][CH:22]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 14487Diisobutylaluminum hydride2×HCID 584453232-[(4-Chloro-phenylsulfanyl)-(2,3,6-trifluoro-phenyl)-methyl]-malonic Acid Dimethyl Ester

Product 1

HCID 584453782-[(4-Chloro-phenylsulfanyl)-(2,3,6-trifluoro-phenyl)-methyl]-propane-1,3-diol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-[(4-Chloro-phenylsulfanyl)-(2,3,6-trifluoro-phenyl)-methyl]-malonic acid dimethyl ester (Example 10, step 3, 11 g, 26.3 mmole) was dissolved in 200 mL THF and DIBAL-H (1M in hexane, 105 mL) was added. The reaction was stirred at room temperature for five hours. Additional DIBAL-H (1M in hexane, 100 mL) was added and the reaction was stirred at 60° C. for three hours. 300 mL water and 300 mL EtOAc were added. The organic layer was washed with 1N HCl solution (2×100 mL), brine (100 mL), dried over Na2SO4 and concentrated. The product was purified by column chromatography (EtOAc/hexane from 0/100 to 50/50 in 45 minutes). Yield: 6.2 g, 65%. 1H NMR (CDCl3 400 MHz) δ 7.28 (d, J=8.1 Hz, 2H), 7.20 (d, J=8.1 Hz, 2H), 7.00 (m, 1H), 6.75 (m, 1H), 4.85 (d, J=11.0 Hz, 1H), 4.36 (dd, J=7.3 and 3.7 Hz, 1H), 4.21 (dd, J=8.1 and 2.9 Hz, 1H), 3.85 (dd, J=8.8 and 2.9 Hz, 1H), 3.49 (m, 1H), 2.46 (m, 1H), 2.22 (br, 1H), 2.10 (br, 1H).

Workup

  1. stirringthe reaction was stirred at 60° C. for three hours
  2. washThe organic layer was washed with 1N HCl solution (2×100 mL), brine (100 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customThe product was purified by column chromatography (EtOAc/hexane from 0/100 to 50/50 in 45 minutes)

Sources & evidence

ORD record
ord-683e824d51c04065b5d6555a73ea8a0a
Source dataset
uspto-grants-2013_10
Patent number
US08569521B2

Reaction notes

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