Diisobutylaluminum hydride → 2-[(4-Chloro-benzenesulfonyl)-(2,3,6-trifluoro-phenyl)-methyl]-propane-1,3-diol

HRID 564306Notes

Reaction equation

HRID 564306 reaction equation
C[O:2][C:3](=O)[CH:4]([CH:9](SC1C=CC(Cl)=CC=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.[Cl:37][C:38]1[CH:39]=[C:40]([CH:45]=[CH:46][CH:47]=1)C(OO)=O.[O-:48][S:49]([O-:51])=O.[Na+].[Na+]>C1COCC1.O>[Cl:37][C:38]1[CH:39]=[CH:40][C:45]([S:49]([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])(=[O:51])=[O:48])=[CH:46][CH:47]=1

Participants

7

Reactant 4

HCID 14487Diisobutylaluminum hydrideHCID 24437Sodium SulfiteHCID 70297m-Chloroperbenzoic acidHCID 584453232-[(4-Chloro-phenylsulfanyl)-(2,3,6-trifluoro-phenyl)-methyl]-malonic Acid Dimethyl Ester

Product 1

HCID 589507082-[(4-Chloro-benzenesulfonyl)-(2,3,6-trifluoro-phenyl)-methyl]-propane-1,3-diol

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

2-[(4-Chloro-phenylsulfanyl)-(2,3,6-trifluoro-phenyl)-methyl]-malonic acid dimethyl ester (7.1 g, 17 mmol) was dissolved in 50 mL THF and DIBAL-H (1M in hexane, 68 mL) was added. The reaction was stirred at room temperature overnight. 100 mL of water was added to quench the reaction and 100 mL EtOAc was added to extract the product. The organic layer washed with 1N HCl solution (2×50 mL), brine (50 mL), dried over Na2SO4 and concentrated. The residue was dissolved in 200 mL DCM and mCPBA (77%, 7.6 g, 34 mmol) was added. The reaction was stirred at room temperature for three hours. 8 g Na2SO3 in 50 mL of water was added to quench excess mCPBA. The organic layer was separated, washed with 1N NaOH solution, brine, dried over Na2SO4 and concentrated. The product was purified by column using EtOAc/hex as the eluent (gradient from 0/100 to 75/25 in 40 min, 2.7 g, 40%). 1H NMR (CDCl3 400 MHz) δ 7.59 (m, 2H), 7.36 (m, 2H), 7.06 (m, 1H), 6.81 (m, 0.5H), 6.57 (m, 0.5H), 5.26 (d, J=11.0 Hz, 1H), 4.65 (m, 1H), 4.20 (dt, J=11.7 and 2.2 Hz, 1H), 3.93 (m, 1H), 3.42 (m, 1H), 3.02 (m, 1H).

Workup

  1. customto quench
  2. customthe reaction and 100 mL EtOAc
  3. additionwas added
  4. extractionto extract the product
  5. washThe organic layer washed with 1N HCl solution (2×50 mL), brine (50 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. dissolutionThe residue was dissolved in 200 mL DCM
  9. stirringThe reaction was stirred at room temperature for three hours
  10. customto quench excess mCPBA
  11. customThe organic layer was separated
  12. washwashed with 1N NaOH solution, brine
  13. dry with materialdried over Na2SO4
  14. concentrationconcentrated
  15. customThe product was purified by column
  16. customas the eluent (gradient from 0/100 to 75/25 in 40 min, 2.7 g, 40%)

Sources & evidence

ORD record
ord-e7ee68f6989d44a387b3b31c37e6eb7c
Source dataset
uspto-grants-2011_11
Patent number
US08067621B2

Reaction notes

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