Benzyl Bromide → (1R*,2R*,5S*,6R*)-8-Benzyl-2-{(1R*)-1-[3,5-bis(trifluoromethyl)phenyl]-2-phenylmethoxyethoxy}-6-cyano-1-phenyl-8-azabicyclo[3.2.1]octane

HRID 2088218Notes

Reaction equation

HRID 2088218 reaction equation
[CH2:1]([N:8]1[C@@H:13]2[C@H:14]([C:16]#[N:17])[CH2:15][C@@:9]1([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[C@H:10]([O:18][C@H:19]([C:22]1[CH:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[C:24]([C:32]([F:35])([F:34])[F:33])[CH:23]=1)[CH2:20][OH:21])[CH2:11][CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:42](Br)[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1.C1OCCOCCOCCOCCOCCOC1.[H-].[Na+]>C1COCC1.O>[CH2:1]([N:8]1[C@@H:13]2[C@H:14]([C:16]#[N:17])[CH2:15][C@@:9]1([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[C@H:10]([O:18][C@H:19]([C:22]1[CH:27]=[C:26]([C:28]([F:30])([F:31])[F:29])[CH:25]=[C:24]([C:32]([F:33])([F:34])[F:35])[CH:23]=1)[CH2:20][O:21][CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[CH2:11][CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 2855718-Crown-6HCID 86586766(1R*,2R*,5S*,6R*)-8-Benzyl-2-{(1R*)-1-[3,5-bis(trifluoromethyl)phenyl]-2-hydroxyethoxy}-6-cyano-1-phenyl-8-azabicyclo[3.2.1]octane

Product 1

HCID 86586768(1R*,2R*,5S*,6R*)-8-Benzyl-2-{(1R*)-1-[3,5-bis(trifluoromethyl)phenyl]-2-phenylmethoxyethoxy}-6-cyano-1-phenyl-8-azabicyclo[3.2.1]octaneYield 79.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

(1R*,2R*,5S*,6R*)-8-Benzyl-2-{(1R*)-1-[3,5-bis(trifluoromethyl)phenyl]-2-hydroxyethoxy}-6-cyano-1-phenyl-8-azabicyclo[3.2.1]octane (Example 156; 0.7749 g, 1.35 mmol), benzyl bromide (0.4618 g, 0.321 ml, 2.7 mmol), 18-crown-6 (0.714 g, 2.7 mmol) and sodium hydride (0.1037 g, 4.32 mmol) in THF (6 ml) were heated at 60° C. for 1 hour. The mixture was diluted with water and extracted into ethyl acetate. The organics were collected and dried (MgSO4) and concentrated in vacuo. The residue was purified by flash column chromatography eluting with 15% ethyl acetate/iso-hexane, to afford the title compound as a clear oil (712 mg, 79%).

Workup

  1. extractionextracted into ethyl acetate
  2. customThe organics were collected
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash column chromatography
  6. washeluting with 15% ethyl acetate/iso-hexane

Sources & evidence

ORD record
ord-136962c30cd84653824da80542e86142
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Reaction notes

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