Lithium borohydride → ((1S,2R,3R,4S)-4-((R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(4-fluorophenyl)cyclohexane-1,2-diyl)dimethanol

HRID 1991361Notes

Reaction equation

HRID 1991361 reaction equation
[F:1][C:2]([F:40])([F:39])[C:3]1[CH:4]=[C:5]([C@H:13]([O:15][C@H:16]2[CH2:21][CH2:20][C@H:19]([C:22](OCC)=[O:23])[C@@H:18]([C:27](OCC)=[O:28])[C@@H:17]2[C:32]2[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=2)[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[Li+].[BH4-]>C1COCC1>[F:12][C:9]([F:10])([F:11])[C:7]1[CH:6]=[C:5]([C@H:13]([O:15][C@H:16]2[CH2:21][CH2:20][C@H:19]([CH2:22][OH:23])[C@@H:18]([CH2:27][OH:28])[C@@H:17]2[C:32]2[CH:33]=[CH:34][C:35]([F:38])=[CH:36][CH:37]=2)[CH3:14])[CH:4]=[C:3]([C:2]([F:1])([F:39])[F:40])[CH:8]=1

Participants

4

Reactant 2

HCID 4148881Lithium borohydrideHCID 42639483HCID 42639483, compound

Product 1

HCID 42639484((1S,2R,3R,4S)-4-((R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(4-fluorophenyl)cyclohexane-1,2-diyl)dimethanolYield 95.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
68 °C

Procedure

To a solution of 9.2 g (15.9 mmol) diethyl (1S,2S,3R,4S)4-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}-3-(4-fluorophenyl)cyclohexane-1,2-dicarboxylate (step F) in 100 mL THF under nitrogen atmosphere at RT was added 2 g (112.4 mmol, excess) LiBH4 powder. The resulting mixture was heated at 68° C. for 2 hr then cooled to RT. The reaction mixture was carefully quenched by the addition of 30 mL water, then extracted with EtOAc. The combined organic extracts were dried over drying agent, filtered and the solvent evaporated under vacuum to give 7.5 g of the crude title compound as an oil which was used without further purification. 1H-NMR (CDCl3): δ: 7.70 (1H, s), 7.20 (2H, s), 7.00 (2H, m), 6.87 (2H, t, J=8.2 Hz), 4.20 (1H, q, J=6.0 Hz), 3.78 (1H, m), 3.67 (1H, m), 3.52 (1H, m), 3.30-3.20 (2H, m), 2.58 (1H, t, J=11.9 Hz), 2.32 (1H, m), 1.87 (1H, m), 1.65 (1H, m), 1.58-1.35 (3H, m), 1.30 (3H, t, J=6.0 Hz).

Workup

  1. temperaturethen cooled to RT
  2. customThe reaction mixture was carefully quenched by the addition of 30 mL water
  3. extractionextracted with EtOAc
  4. customThe combined organic extracts were dried
  5. customover drying agent
  6. filtrationfiltered
  7. customthe solvent evaporated under vacuum

Sources & evidence

ORD record
ord-dec78a3bf7024f4bbdc1769244db4224
Source dataset
uspto-grants-2010_01
Patent number
US07645790B2

Reaction notes

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