Methanol → HCID 69890918, compound

HRID 2088106Notes

Reaction equation

HRID 2088106 reaction equation
[CH2:1]([N:8]1[C@@H:13]2[C@@H:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:15][C@@:9]1([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:10](=[O:23])[CH2:11][CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CO.[BH4-].[Na+]>C1COCC1>[CH2:1]([N:8]1[C@@H:13]2[C@@H:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:15][C@@:9]1([C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)[C@@H:10]([OH:23])[CH2:11][CH2:12]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 4311764Sodium borohydrideHCID 69891741(1R*,5S*,6S*)-8-Benzyl-6-(tert-butoxycarbonyl)-1-phenyl-8-azabicyclo[3.2.1]octan-2-one

Product 1

HCID 69890918HCID 69890918, compoundYield 8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(1R*,5S*,6S*)-8-Benzyl-6-(tert-butoxycarbonyl)-1-phenyl-8-azabicyclo[3.2.1]octan-2-one (Description 19b; 750 mg, 1.91 mmol) was dissolved in THF (5 ml) and methanol (25 ml) was added. The mixture was cooled to +5° C. and treated with sodium borohydride (184 mg, 4.8 mmol). The reaction mixture was stirred for 45 minutes, quenched with saturated aqueous NH4Cl (10 ml) and concentrated in vacuo. The aqueous residue was extracted with dichloromethane. The combined organic extracts were dried (Na2SO4) and concentrated to give crude product as a 10:1 mixture of diastereoisomers. The residue was purified by chromatography on silica gel (iso-hexane:diethyl ether 0-30%) to give the (1R*,2R*,5S*,6S*)-isomer (710 mg, 92%) and the (1R*,2S*,5S*,6S*)-isomer (59 mg, 8%) of the title compound.

Workup

  1. temperatureThe mixture was cooled to +5° C.
  2. customquenched with saturated aqueous NH4Cl (10 ml)
  3. concentrationconcentrated in vacuo
  4. extractionThe aqueous residue was extracted with dichloromethane
  5. dry with materialThe combined organic extracts were dried (Na2SO4)
  6. concentrationconcentrated
  7. customto give crude product
  8. additionas a 10:1 mixture of diastereoisomers
  9. customThe residue was purified by chromatography on silica gel (iso-hexane:diethyl ether 0-30%)
  10. customto give the (1R*,2R*,5S*,6S*)-isomer (710 mg, 92%)

Sources & evidence

ORD record
ord-bb176cdb70a947c6a13fb62b5388115c
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Reaction notes

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