Sodium hydride → HCID 44140173, compound

HRID 1244697Notes

Reaction equation

HRID 1244697 reaction equation
[H-].[Na+].[C:3]([O:7][C:8](=[O:37])[NH:9][C@@H:10]1[C@@H:27]([NH:28][C:29](=[O:36])[CH2:30][CH:31]([CH2:34]Cl)[CH2:32][F:33])[CH2:26][N:13]2[CH2:14][CH2:15][C:16]3[C:21]([C@@H:12]2[CH2:11]1)=[CH:20][C:19]([O:22][CH3:23])=[C:18]([O:24][CH3:25])[CH:17]=3)([CH3:6])([CH3:5])[CH3:4]>CN(C)C=O>[C:3]([O:7][C:8](=[O:37])[NH:9][C@@H:10]1[C@@H:27]([N:28]2[CH2:34][C@@H:31]([CH2:32][F:33])[CH2:30][C:29]2=[O:36])[CH2:26][N:13]2[CH2:14][CH2:15][C:16]3[C:21]([C@@H:12]2[CH2:11]1)=[CH:20][C:19]([O:22][CH3:23])=[C:18]([O:24][CH3:25])[CH:17]=3)([CH3:6])([CH3:5])[CH3:4]

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 68621995HCID 68621995, compound

Product 1

HCID 44140173HCID 44140173, compoundYield 38.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (55–65% dispersion in oil, 1.14 g, 28.5 mmol) was added to a suspension of [(S,S,S)-3-(3-chloromethyl-4-fluoro-butyrylamino)-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-yl]-carbamic acid tert-butyl ester (6.72 g, 13.1 mmol) in N,N-dimethylformamide (95 mL) at r.t., then after 1 h the reaction mixture was poured onto ice and partitioned between ethyl acetate and water. The organic layer was washed with brine, dried (MgSO4), and evaporated. Chromatography (SiO2, cyclohexane/2-propanol 4:1) afforded [(S,S,S)-3-((S)-4-fluoromethyl-2-oxo-pyrrolidin-1-yl)-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-yl]-carbamic acid tert-butyl ester (2.40 g, 38%) and the epimer, [(S,S,S)-3-((R)-4-fluoromethyl-2-oxo-pyrrolidin-1-yl)-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido [2,1-a]isoquinolin-2-yl]-carbamic acid tert-butyl ester (2.73 g, 44%).

Workup

  1. additionafter 1 h the reaction mixture was poured onto ice
  2. custompartitioned between ethyl acetate and water
  3. washThe organic layer was washed with brine
  4. dry with materialdried (MgSO4)
  5. customevaporated

Sources & evidence

ORD record
ord-db80435a29dc4d5cb8cb781c8945daf6
Source dataset
uspto-grants-2006_10
Patent number
US07122555B2

Reaction notes

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