4-Methylmorpholine → (2S,4S)-4-acetylthio-1-(4-nitrobenzyloxycarbonyl)-2-(3-(4-nitrobenzyloxycarbonylmethylaminocarbonyl)phenylcarbamoyl)-pyrrolidine

HRID 260314Notes

Reaction equation

HRID 260314 reaction equation
[C:1]([S:4][C@@H:5]1[CH2:9][N:8]([C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=2)=[O:11])[C@H:7]([C:23](=[O:34])[NH:24][C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([OH:33])=O)[CH:26]=2)[CH2:6]1)(=[O:3])[CH3:2].C(Cl)(=O)C(Cl)=O.Cl.[NH2:42][CH2:43][C:44]([O:46][CH2:47][C:48]1[CH:53]=[CH:52][C:51]([N+:54]([O-:56])=[O:55])=[CH:50][CH:49]=1)=[O:45].CN1CCOCC1>ClCCl.CN(C)C=O>[C:1]([S:4][C@@H:5]1[CH2:9][N:8]([C:10]([O:12][CH2:13][C:14]2[CH:15]=[CH:16][C:17]([N+:20]([O-:22])=[O:21])=[CH:18][CH:19]=2)=[O:11])[C@H:7]([C:23](=[O:34])[NH:24][C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([NH:42][CH2:43][C:44]([O:46][CH2:47][C:48]3[CH:53]=[CH:52][C:51]([N+:54]([O-:56])=[O:55])=[CH:50][CH:49]=3)=[O:45])=[O:33])[CH:26]=2)[CH2:6]1)(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 65578Oxalyl chloride2×HCID 22401149Glycine p-nitrobenzyl ester hydrochlorideHCID 57213936(2S,4S)-4-acetylthio-1-(4-nitrobenzyloxycarbonyl)-2-(3-carboxyphenylcarbamoyl)pyrrolidine

Product 1

HCID 57286643(2S,4S)-4-acetylthio-1-(4-nitrobenzyloxycarbonyl)-2-(3-(4-nitrobenzyloxycarbonylmethylaminocarbonyl)phenylcarbamoyl)-pyrrolidineYield 55.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalyst2×HCID 6344DichloromethaneSolvent4×

Procedure

To a solution of (2S,4S)-4-acetylthio-1-(4-nitrobenzyloxycarbonyl)-2-(3-carboxyphenylcarbamoyl)pyrrolidine (0.49 g, 1 mM) in dichloromethane (10 ml) was added oxalyl chloride (0.20 ml. 1.1 mM) and dimethylformamide (2-3 drops). After 1 hour a further amount of oxalyl chloride (0.20 ml, 1.1 mM) and DMF (2-3 drops) were added and the mixture stirred for a further hour. The solution was evaporated to leave a yellow gum. The gum was dissolved in dichloromethane (10 ml) and added to a suspension of 4-nitrobenzyl 2-aminoethanoate hydrochloride salt (0.30 g, 1.2 mM) and N-methylmorpholine (0.27 ml, 2.4 mM) in dichloromethane (10 ml). After 17 hours the mixture was diluted with dichloromethane (80 ml), washed with water (20 ml), brine (20 ml) and dried (MgSO4). Purification by flash chromatography through silica using a gradient of dichloromethane to ethyl acetate as eluent gave (2S,4S)-4-acetylthio-1-(4-nitrobenzyloxycarbonyl)-2-(3-(4-nitrobenzyloxycarbonylmethylaminocarbonyl)phenylcarbamoyl)-pyrrolidine (380 mg).

Workup

  1. customThe solution was evaporated
  2. customto leave a yellow gum
  3. washwashed with water (20 ml), brine (20 ml)
  4. dry with materialdried (MgSO4)
  5. customPurification by flash chromatography through silica using a gradient of dichloromethane to ethyl acetate as eluent

Sources & evidence

ORD record
ord-65144a5d56fa4bf49870ae86bbac6abd
Source dataset
uspto-grants-1996_06
Patent number
US05527791

Reaction notes

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