Sodium hydride → HCID 86586772, compound

HRID 2088222Notes

Reaction equation

HRID 2088222 reaction equation
[H-].[Na+].[CH2:3]([N:10]1[C@@H:15]2[C@@:16]([C:19]([O:21][CH2:22][CH3:23])=[O:20])([F:18])[CH2:17][C@@:11]1([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C@H:12]([OH:24])[CH2:13][CH2:14]2)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[F:31][C:32]([F:46])([F:45])[C:33]1[CH:34]=[C:35]([CH:38]=[C:39]([C:41]([F:44])([F:43])[F:42])[CH:40]=1)[CH2:36]Br.C1OCCOCCOCCOCCOCCOC1>CCCC(C)C.C1COCC1>[CH2:3]([N:10]1[C@@H:15]2[C@@:16]([C:19]([O:21][CH2:22][CH3:23])=[O:20])([F:18])[CH2:17][C@@:11]1([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C@H:12]([O:24][CH2:36][C:35]1[CH:38]=[C:39]([C:41]([F:43])([F:44])[F:42])[CH:40]=[C:33]([C:32]([F:31])([F:45])[F:46])[CH:34]=1)[CH2:13][CH2:14]2)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 2855718-Crown-6HCID 1225733,5-Bis(trifluoromethyl)benzyl bromideHCID 69889515HCID 69889515, compound

Product 1

HCID 86586772HCID 86586772, compoundYield 62.3%

Reagents, catalysts & solvents 2

HCID 78922-MethylpentaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Sodium hydride (60% in oil, 100 mg, 2.5 mmol) was washed twice with iso-hexane and added as a suspension in THF (3 ml) to a stirred mixture of (1R*,2R*,5S*,6S*)-8-benzyl-6-ethoxycarbonyl-6-fluoro-1-phenyl-8-azabicyclo[3.2.1]octan-2-ol (Description 38; 512 mg, 1.3 mmol), 3,5-bis(trifluoromethyl)benzyl bromide (0.5 ml, 2.7 mmol), 18-crown-6 (360 mg, 1.37 mmol) in THF (5 ml) at room temperature. The reaction mixture was stirred for 40 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) to give the title compound (494 mg, 61%).

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)

Sources & evidence

ORD record
ord-dcd71f30d1fb4dddb7cef42ad39e3372
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Reaction notes

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