Hydrochloric Acid → (3,5-Difluoro-4-(methylthio)phenyl)methanol

HRID 47645Notes

Reaction equation

HRID 47645 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([F:12])[C:9]=1[S:10][CH3:11])[CH:5]=[O:6].[BH4-].[Na+].Cl.O>C1COCC1>[F:12][C:8]1[CH:7]=[C:4]([CH2:5][OH:6])[CH:3]=[C:2]([F:1])[C:9]=1[S:10][CH3:11]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 4311764Sodium borohydrideHCID 227466823,5-Difluoro-4-(methylthio)benzaldehyde

Product 1

HCID 22746033(3,5-Difluoro-4-(methylthio)phenyl)methanolYield 78.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3,5-difluoro-4-(methylthio)-benzaldehyde (31.3 g, 0.166 mol) in anhydrous THF (200 mL) cooled with a cold water bath was added sodium borohydride (1.6 g, 0.042 mol) in portions over 30 minutes. After stirring 1 hour at room temperature, excess dilute HCl was added, until gas evolution ceased. Water (600 mL) was added and the mixture extracted with dichloromethane (1×500 mL, 1×100 mL). The combined extracts were washed once with water, dried with magnesium sulfate, and concentrated. Purification by silica gel chromatography using 3% ethyl acetate/10% dichloromethane in hexanes initially, and eluting product with 60% ethyl acetate in hexanes gave [3,5-difluoro-4-(methylthio)-phenyl]methanol as a light yellow liquid (24.8 g, 78%). 1H NMR (CDCl3/400 MHz) 6.88-6.93 (m, 2H), 4.65 (s, 2H), 2.42 (s, 3H). HRMS m/z 190.0266 (M+H+, calcd 190.0264).

Workup

  1. extractionthe mixture extracted with dichloromethane (1×500 mL, 1×100 mL)
  2. washThe combined extracts were washed once with water
  3. dry with materialdried with magnesium sulfate
  4. concentrationconcentrated
  5. customPurification by silica gel chromatography
  6. washeluting product with 60% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-d39e4c47ef9b46cbad4614e5f3e8987e
Source dataset
uspto-grants-2004_03
Patent number
US06699884B2

Reaction notes

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