Imidazole → HCID 66704803, compound

HRID 859900Notes

Reaction equation

HRID 859900 reaction equation
[CH:1]1([NH:4][C:5]([C@@H:7]2[C@H:11]([CH2:12][OH:13])[CH2:10][N:9]([C@H:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH3:15])[CH2:8]2)=[O:6])[CH2:3][CH2:2]1.N1C=CN=C1.[C:27]([Si:31](Cl)([CH3:33])[CH3:32])([CH3:30])([CH3:29])[CH3:28]>CN(C)C=O>[CH:1]1([NH:4][C:5]([C@@H:7]2[C@H:11]([CH2:12][O:13][Si:31]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:33])[CH3:32])[CH2:10][N:9]([C@H:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH3:15])[CH2:8]2)=[O:6])[CH2:2][CH2:3]1

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 66705180HCID 66705180, compound

Product 1

HCID 66704803HCID 66704803, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(3R,4S)-N-Cyclopropyl-4-hydroxymethyl-1-[(1S)-1-phenylethyl]pyrrolidine-3-carboxamide (7.54 g) was dissolved in N,N-dimethylformamide (180 mL). While this solution was cooled on an ice bath, imidazole (2.67 g) and tert-butylchlorodimethylsilane (4.72 g) were sequentially added. The mixture was stirred at room temperature for 90 min and was subsequently concentrated under reduced pressure. The resulting residue was dissolved in ethyl acetate (300 mL) and the solution was washed with water (2×100 mL), followed by drying over anhydrous sodium sulfate and concentration under reduced pressure. The resulting residue was purified on a silica gel column (eluant=ethyl acetate) to give 7.05 g of (3R,4S)-N-cyclopropyl-4-(tert-butyldimethylsilyl)oxymethyl-1-[(1S)-1-phenylethyl]pyrrolidine-3-carboxamide as a pale yellow tar-like product.

Workup

  1. temperatureWhile this solution was cooled on an ice bath
  2. concentrationwas subsequently concentrated under reduced pressure
  3. dissolutionThe resulting residue was dissolved in ethyl acetate (300 mL)
  4. washthe solution was washed with water (2×100 mL)
  5. dry with materialby drying over anhydrous sodium sulfate and concentration under reduced pressure
  6. customThe resulting residue was purified on a silica gel column (eluant=ethyl acetate)

Sources & evidence

ORD record
ord-f934c435a283415880bc94e5ef8ab39c
Source dataset
uspto-grants-2006_12
Patent number
US07153851B2

Reaction notes

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