Phosgene → 4-[(1S,7S,7aR)-7-tert-Butyldimethylsilanoxy-1-methyl-3-oxo-hexahydro-pyrrolo[1,2-c]imidazol-2-yl]-2-chloro-3-methylbenzonitrile

HRID 751135Notes

Reaction equation

HRID 751135 reaction equation
[Si:1]([O:8][C@H:9]1[CH2:13][CH2:12][NH:11][C@@H:10]1[C@@H:14]([NH:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]#[N:24])=[C:19]([Cl:25])[C:18]=1[CH3:26])[CH3:15])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.[C:36](Cl)(Cl)=[O:37]>C(Cl)Cl.C1(C)C=CC=CC=1>[O:8]([C@@H:9]1[C@@H:10]2[N:11]([C:36](=[O:37])[N:16]([C:17]3[CH:22]=[CH:21][C:20]([C:23]#[N:24])=[C:19]([Cl:25])[C:18]=3[CH3:26])[C@H:14]2[CH3:15])[CH2:12][CH2:13]1)[Si:1]([C:4]([CH3:6])([CH3:7])[CH3:5])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 6371PhosgeneHCID 81531DiisopropylethylamineHCID 66863531HCID 66863531, compound

Product 1

HCID 167337644-[(1S,7S,7aR)-7-tert-Butyldimethylsilanoxy-1-methyl-3-oxo-hexahydro-pyrrolo[1,2-c]imidazol-2-yl]-2-chloro-3-methylbenzonitrile

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of crude 61I (˜1.81 mmol) in CH2Cl2 (10 mL) was added i-Pr2NEt (2 mL) followed by 20% phosgene in toluene (2.5 mL) dropwise. The reaction was stirred at rt overnight. Reaction was extracted with EtOAc (50 mL) which was washed twice with 1N HCl and then saturated NaHCO3. The organic layer was dried over MgSO4, filtered and concentrated. Purification by flash chromatography (silica gel, 0 to 10% EtOAc in hexane) provided the title compound (369 mg): MS (ES) m/z 420.23 [M+H]+

Workup

  1. customReaction
  2. extractionwas extracted with EtOAc (50 mL) which
  3. washwas washed twice with 1N HCl
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by flash chromatography (silica gel, 0 to 10% EtOAc in hexane)

Sources & evidence

ORD record
ord-f3d0d4d7a7074298b2ae4efdcb017df6
Source dataset
uspto-grants-2008_07
Patent number
US07405234B2

Reaction notes

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