Triethylamine → 4-acetylamino-5-chloro-2-methoxy-N-[(2S,4S)-1-acetyl-2-hydroxymethyl-4-pyrrolidinyl]benzamide

HRID 1723904Notes

Reaction equation

HRID 1723904 reaction equation
[C:1]([NH:4][C:5]1[C:13]([Cl:14])=[CH:12][C:8]([C:9]([OH:11])=O)=[C:7]([O:15][CH3:16])[CH:6]=1)(=[O:3])[CH3:2].C(N(CC)CC)C.C(Cl)(=O)OCC.[C:30]([N:33]1[CH2:37][C@@H:36]([NH2:38])[CH2:35][C@H:34]1[CH2:39][OH:40])(=[O:32])[CH3:31]>ClCCl.O>[C:1]([NH:4][C:5]1[C:13]([Cl:14])=[CH:12][C:8]([C:9]([NH:38][C@@H:36]2[CH2:37][N:33]([C:30](=[O:32])[CH3:31])[C@H:34]([CH2:39][OH:40])[CH2:35]2)=[O:11])=[C:7]([O:15][CH3:16])[CH:6]=1)(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 109884964-Acetamido-5-chloro-2-methoxybenzoic acidHCID 450861111-((2S,4S)-4-Amino-2-(hydroxymethyl)pyrrolidin-1-yl)ethanone

Product 1

HCID 117406984-acetylamino-5-chloro-2-methoxy-N-[(2S,4S)-1-acetyl-2-hydroxymethyl-4-pyrrolidinyl]benzamideYield 75.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

9.84 g of 4-acetylamino-5-chloro-2-methoxybenzoic acid, and 4.5 g of triethylamine were dissolved in 40 ml of dichloromethane, and 4.60 g of ethyl chlorocarbonate was added dropwise to the solution at not higher than 10° C. After stirring at the same temperature for 30 minutes, a solution of 7.03 g of (2S,4S)-(−)-1-acetyl-4-amino-2-hydroxymethylpyrrolidine in dichloromethane (20 ml) was added dropwise. After stirring at the same temperature overnight, water (20 ml) was added, precipitated crystals were filtered, and the resulting crystals were dried in a warm air at 50 to 55° C. to obtain 11.74 g of 4-acetylamino-5-chloro-2-methoxy-N-[(2S,4S)-1-acetyl-2-hydroxymethyl-4-pyrrolidinyl]benzamide.

Workup

  1. additionwas added
  2. customprecipitated crystals
  3. filtrationwere filtered
  4. customthe resulting crystals were dried in a warm air at 50 to 55° C.

Sources & evidence

ORD record
ord-a6d4b715b88c4437a32da0ff07774102
Source dataset
uspto-grants-2009_02
Patent number
US07485665B2

Reaction notes

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