Sodium borohydride → HCID 67159214, compound

HRID 1892000Notes

Reaction equation

HRID 1892000 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH3:19])[C:13](=[O:14])[CH2:12][CH2:11][CH:10]([C:15](OC)=[O:16])[CH2:9]2)=[CH:4][C:3]=1[C:20]([F:23])([F:22])[F:21].[BH4-].[Na+]>C(O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH3:19])[CH2:9][CH:10]([CH2:15][OH:16])[CH2:11][CH2:12][CH:13]2[OH:14])=[CH:4][C:3]=1[C:20]([F:21])([F:22])[F:23]

Participants

4

Reactant 2

HCID 4311764Sodium borohydride2×HCID 44612585HCID 44612585, compound

Product 1

HCID 67159214HCID 67159214, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

A solution of methyl (1RS,3RS)-3-(4-chloro-3-(trifluoromethyl)phenyl)-3-methyl-4-oxocyclohexane-carboxylate (1.348 g, 3.87 mmol) in ethanol (20 mL) was treated with sodium borohydride (0.292 g, 7.73 mmol) and stirred at 60° C. Additional sodium borohydride (100 mg) was added after 7 h and again after 22.75 h. After 28 h, the resulting mixture was concentrated under vacuum and the resulting residue was stirred with ethyl acetate and saturated aqueous sodium bicarbonate for 30 min. The aqueous and organic layers were separated and the aqueous phase was extracted with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated under vacuum to yield a residue. This residue was purified by column chromatography on silica gel, eluting with 30-70% ethyl acetate-hexanes, to provide (1RS,2RS,4RS)-2-(4-chloro-3-(trifluoromethyl)phenyl)-4-(hydroxymethyl)-2-methylcyclohexanol as a white glassy foam (967 mg, 78%). 1H NMR (500 MHz, CDCl3) δ 8.14 (d, J=2.2 Hz, 1 H), 7.82 (dd, J=8.5, 2.2 Hz, 1 H), 7.41 (d, J=8.8 Hz, 1 H), 3.76 (dd, J=12.1, 3.8 Hz, 1 H), 3.45 (ab portion of abx, 2 H), 2.37 (dt, J=14.3, 2.7 Hz, 1 H), 1.92 (br. s, 1 H), 1.82 (m, 1 H), 1.77 (m, 1 H), 1.58 (m, 3 H), 1.35 (s, 3 H), 1.18 (m, J=14.0, 12.4 Hz, 2H).

Workup

  1. concentrationthe resulting mixture was concentrated under vacuum
  2. stirringthe resulting residue was stirred with ethyl acetate and saturated aqueous sodium bicarbonate for 30 min
  3. customThe aqueous and organic layers were separated
  4. extractionthe aqueous phase was extracted with ethyl acetate
  5. dry with materialThe combined organic phases were dried over sodium sulfate
  6. concentrationconcentrated under vacuum
  7. customto yield a residue
  8. customThis residue was purified by column chromatography on silica gel
  9. washeluting with 30-70% ethyl acetate-hexanes

Sources & evidence

ORD record
ord-effb741ff38645209e85af06682bf73c
Source dataset
uspto-grants-2013_08
Patent number
US08507559B2

Reaction notes

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