Lithium tri-s-butylborohydride → (1R,2S,4S)-4-(dibenzylamino)-2-methylcyclohexanol (1S,2R,4R)-4-(dibenzylamino)-2-methylcyclohexanol

HRID 1623330Notes

Reaction equation

HRID 1623330 reaction equation
[CH2:1]([N:8]([CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C@H:9]1[CH2:14][CH2:13][C:12](=[O:15])[C@@H:11]([CH3:16])[CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:24]([N:31]([CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[C@@H:32]1[CH2:37][CH2:36][C:35](=[O:38])[C@H:34]([CH3:39])[CH2:33]1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.CCC(C)[BH-](C(C)CC)C(C)CC.[Li+]>C1COCC1.[OH-].[Na+]>[CH2:17]([N:8]([CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C@H:9]1[CH2:14][CH2:13][C@@H:12]([OH:15])[C@@H:11]([CH3:16])[CH2:10]1)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1.[CH2:40]([N:31]([CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C@@H:32]1[CH2:37][CH2:36][C@H:35]([OH:38])[C@H:34]([CH3:39])[CH2:33]1)[C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1

Participants

5

Reactant 2

HCID 3611392Lithium tri-s-butylborohydrideHCID 86650615(2S,4S)-4-(dibenzylamino)-2-methylcyclohexanone (2R,4R)-4-(dibenzylamino)-2-methylcyclohexanone

Product 1

HCID 68277691(1R,2S,4S)-4-(dibenzylamino)-2-methylcyclohexanol (1S,2R,4R)-4-(dibenzylamino)-2-methylcyclohexanol

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of (2S,4S)-4-(dibenzylamino)-2-methylcyclohexanone/(2R,4R)-4-(dibenzylamino)-2-methylcyclohexanone (3.1 g, 10.08 mmol) in THF (55 mL) at −78° C. was added L-selectride (15.13 mL, 15.13 mmol) dropwise. After stirring for 5 min at −78° C. the mixture was allowed to warm up to 0° C. Stirring was continued for 18 hr as the reaction mixture was warmed from 0° C. to ambient temperature. The mixture was diluted carefully with 1N aq NaOH (15 mL) and stirred vigorously for 3 hr. The mixture was extracted with EtOAc (3ט100 mL). The combined organic layers were washed with brine (˜100 mL), dried over Na2SO4, filtered off and concentrated in vacuo. The resulting residue was purified by column chromatography [SiO2, 120 g, EtOAc/hexane=0/100 to 20/80 over-25 min; EtOAc/hexane=20/80 to 40/60 over 5 min] providing (1R,2S,4S)-4-(dibenzylamino)-2-methylcyclohexanol/(1S,2R,4R)-4-(dibenzylamino)-2-methylcyclohexanol as a colorless liquid. Yield: 2.83 g. LCMS (m/z): 310.3 [M+H]+; Retention time=0.66 min.

Workup

  1. temperatureto warm up to 0° C
  2. stirringStirring
  3. waitwas continued for 18 hr as the reaction mixture
  4. temperaturewas warmed from 0° C. to ambient temperature
  5. stirringstirred vigorously for 3 hr
  6. extractionThe mixture was extracted with EtOAc (3ט100 mL)
  7. washThe combined organic layers were washed with brine (˜100 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered off
  10. concentrationconcentrated in vacuo
  11. customThe resulting residue was purified by column chromatography [SiO2, 120 g, EtOAc/hexane=0/100 to 20/80 over-25 min; EtOAc/hexane=20/80 to 40/60 over 5 min]

Sources & evidence

ORD record
ord-89ce5ee17c0f46719e1e3055e2371bc7
Source dataset
uspto-grants-2014_07
Patent number
US08778951B2

Reaction notes

Loading…