Dimethyl Sulfoxide → HCID 86628531, compound

HRID 732648Notes

Reaction equation

HRID 732648 reaction equation
CS(C)=O.C(Cl)(=O)C(Cl)=O.[OH:11][CH2:12][C@@H:13]1[C@@H:17]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[CH:19]=2)[CH2:16][N:15]([C:28](=[O:43])[CH2:29][CH2:30][CH2:31][CH2:32][C:33]([O:35][CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[O:34])[CH2:14]1.C(N(CC)CC)C>ClCCl>[CH:12]([C@@H:13]1[C@@H:17]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:25])([F:26])[F:27])[CH:19]=2)[CH2:16][N:15]([C:28](=[O:43])[CH2:29][CH2:30][CH2:31][CH2:32][C:33]([O:35][CH2:36][C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)=[O:34])[CH2:14]1)=[O:11]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 68914570HCID 68914570, compound

Product 1

HCID 86628531HCID 86628531, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A 0.30 ml portion of DMSO was dissolved in 5 ml of dichloromethane, and 0.18 ml of oxalyl chloride was added thereto while keeping the internal temperature at −60° C. or less. After 30 minutes of stirring, a dichloromethane solution (5 ml) of 323 mg of benzyl 6-{(3R,4S)-3-(hydroxymethyl)-4-[3-(trifluoromethyl)phenyl]pyrrolidin-1-yl}-6-oxohexanoate was added thereto while keeping the internal temperature at −60° C. or less, successively stirring this for 30 minutes. The reaction solution was mixed with 0.87 ml of triethylamine while keeping the internal temperature at −50° C. or less, and then stirred at −78° C. for 4.5 hours. Thereafter, work-up was carried out in the standard method to obtain benzyl 6-{(3R,4S)-3-formyl-4-[3-(trifluoromethyl)phenyl]pyrrolidin-1-yl}-6-oxohexanoate as a crude product. A mixture of the thus obtained crude product, 143 mg of (R)-(+)-1-(1-naphthyl)ethylamine, acetic acid and 5 ml of 1,2-dichloroethane was stirred for 20 minutes, and then mixed with 443 mg of sodium triacetoxyborohydride at room temperature and stirred at room temperature for 17Hours, successively carrying out work-up and purification in the standard method to obtain 312 mg of benzyl 6-{(3S,4S)-3-({[(1R)-1-(naphthyl)ethyl]amino}methyl)-4-[3-(trifluoromethyl)phenyl]pyrrolidin-1-yl}-6-oxohexanoate.

Workup

  1. customat −60° C. or less
  2. customat −60° C. or less
  3. stirringsuccessively stirring this for 30 minutes
  4. customat −50° C. or less
  5. stirringstirred at −78° C. for 4.5 hours

Sources & evidence

ORD record
ord-32320780e9014c4cbbdddcae7c7190a5
Source dataset
uspto-grants-2009_09
Patent number
US07585886B2

Reaction notes

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