Isopropylamine → rac-isopropyl-carbamic acid (1R*,2R*,4R*)-2-(2-{[3-(4-methoxy-1H-benzoimidazol-2-yl)-propyl]-methyl-amino}-ethyl)-5-phenyl-bicyclo[2.2.2]oct-5-en-2-yl ester

HRID 220303Notes

Reaction equation

HRID 220303 reaction equation
[CH3:1][O:2][C:3]1[C:11]2[N:10]=[C:9]([CH2:12][CH2:13][CH2:14][N:15]([CH3:33])[CH2:16][CH2:17][C:18]3([OH:32])[CH2:23][CH:22]4[CH2:24][CH2:25][CH:19]3[CH:20]=[C:21]4[C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[NH:8][C:7]=2[CH:6]=[CH:5][CH:4]=1.[H-].[Na+].[C:36]([N:43]1[CH:47]=[CH:46]N=C1)(N1C=CN=C1)=[O:37].[CH:48](N)(C)C>C1COCC1>[CH3:1][O:2][C:3]1[C:11]2[N:10]=[C:9]([CH2:12][CH2:13][CH2:14][N:15]([CH3:33])[CH2:16][CH2:17][C@:18]3([O:32][C:36](=[O:37])[NH:43][CH:47]([CH3:46])[CH3:48])[CH2:23][C@H:22]4[CH2:24][CH2:25][C@@H:19]3[CH:20]=[C:21]4[C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)[NH:8][C:7]=2[CH:6]=[CH:5][CH:4]=1

Participants

6

Reactant 4

HCID 6363IsopropylamineHCID 24758Sodium hydrideHCID 682631,1'-CarbonyldiimidazoleHCID 68412969rac-(1R*,2R*,4R*)-2-(2-{[3-(4-methoxy-1H-benzoimidazol-2-yl)-propyl]-methyl-amino}-ethyl)-5-phenyl-bicyclo[2.2.2]oct-5-en-2-ol

Product 1

HCID 90802441rac-isopropyl-carbamic acid (1R*,2R*,4R*)-2-(2-{[3-(4-methoxy-1H-benzoimidazol-2-yl)-propyl]-methyl-amino}-ethyl)-5-phenyl-bicyclo[2.2.2]oct-5-en-2-yl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 91 mg of rac-(1R*,2R*,4R*)-2-(2-{[3-(4-methoxy-1H-benzoimidazol-2-yl)-propyl]-methyl-amino}-ethyl)-5-phenyl-bicyclo[2.2.2]oct-5-en-2-ol in 2 mL of anh. THF were added 57 mg of NaH at −10° C. The suspension was stirred for 45 min allowing the temperature to reach 0° C. 171 mg of 1,1′-carbonyldiimidazole were added at −10° C. and the mixture stirred for 30 min at rt. 0.178 mL of isopropyl amine was added at 0° C. and the reaction mixture stirred overnight at rt. After quenching with sat. NaHCO3 and extracting with DCM, the organic phase was dried over anh. Na2SO4 and concentrated in vacuo. The crude product was purified by prep. TLC using chloroform/MeOH/NEt3 70/30/1 to yield 45 mg of rac-isopropyl-carbamic acid (1R*,2R*,4R*)-2-(2-{[3-(4-methoxy-1H-benzoimidazol-2-yl)-propyl]-methyl-amino}-ethyl)-5-phenyl-bicyclo[2.2.2]oct-5-en-2-yl ester as yellowish oil.

Workup

  1. customto reach 0° C
  2. stirringthe mixture stirred for 30 min at rt
  3. stirringthe reaction mixture stirred overnight at rt
  4. customAfter quenching with sat. NaHCO3
  5. extractionextracting with DCM
  6. dry with materialthe organic phase was dried over anh. Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by prep

Sources & evidence

ORD record
ord-acc23bfe9b044b859c8ffa6da84763c0
Source dataset
uspto-grants-2012_06
Patent number
US08202885B2

Reaction notes

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