Sodium hydride → HCID 86586645, compound

HRID 2088107Notes

Reaction equation

HRID 2088107 reaction equation
[H-].[Na+].[CH2:3]([N:10]1[C@@H:15]2[C@@H:16]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:17][C@@:11]1([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C@H:12]([OH:25])[CH2:13][CH2:14]2)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[F:32][C:33]([F:47])([F:46])[C:34]1[CH:35]=[C:36]([CH:39]=[C:40]([C:42]([F:45])([F:44])[F:43])[CH:41]=1)[CH2:37]Br>CN(C)C=O>[CH2:3]([N:10]1[C@@H:15]2[C@@H:16]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:17][C@@:11]1([C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)[C@H:12]([O:25][CH2:37][C:36]1[CH:39]=[C:40]([C:42]([F:44])([F:45])[F:43])[CH:41]=[C:34]([C:33]([F:32])([F:46])[F:47])[CH:35]=1)[CH2:13][CH2:14]2)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 1225733,5-Bis(trifluoromethyl)benzyl bromideHCID 69889406HCID 69889406, compound

Product 1

HCID 86586645HCID 86586645, compoundYield 121.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60% in oil, 110 mg, 2.75 mmol) was added to a stirred mixture of (1R*,2R*,5S*,6S*)-8-benzyl-6-(tert-butoxycarbonyl)-1-phenyl-8-azabicyclo[3.2.1]octan-2-ol (Description 21a; 670 mg, 1.1 mmol), 3,5-bis(trifluoromethyl)benzyl bromide (1 ml, 5.45 mmol) in N,N-dimethylformamide (5 ml) at room temperature. The reaction mixture was stirred for 20 hours, quenched with saturated aqueous NH4Cl and extracted into a 1:1 mixture of iso-hexane:diethyl ether. The combined organic extracts were washed with water, dried (Na2SO4) and concentrated. The residue was purified by chromatography on silica gel (iso-hexane:diethyl ether 0-5%) to give the title compound (826 mg, 78%).

Workup

  1. customquenched with saturated aqueous NH4Cl
  2. extractionextracted into a 1:1 mixture of iso-hexane
  3. washThe combined organic extracts were washed with water
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customThe residue was purified by chromatography on silica gel (iso-hexane:diethyl ether 0-5%)

Sources & evidence

ORD record
ord-fb710c8ce331401bad73cf824bd6643d
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Reaction notes

Loading…