4-Methylmorpholine → Chloro-N,N-dimethylformiminium chloride

HRID 1736357Notes

Reaction equation

HRID 1736357 reaction equation
[C:1]([Cl:6])(=O)C([Cl:4])=O.[C:7]([S:10][C@@H:11]1[CH2:15][N:14]([C:16]([O:18][CH2:19][CH:20]=[CH2:21])=[O:17])[C@H:13]([C:22]([OH:24])=O)[CH2:12]1)(=[O:9])[CH3:8].CN1CCOCC1.[CH2:32]([O:35][C:36]1[CH:37]=[C:38]([CH:45]=[CH:46][C:47]=1[NH2:48])[C:39]([O:41][CH2:42][CH:43]=[CH2:44])=[O:40])[CH:33]=[CH2:34]>ClCCl.CN(C=O)C>[CH3:13][N+:14]([CH3:15])=[CH:1][Cl:6].[Cl-:4].[C:7]([S:10][C@@H:11]1[CH2:15][N:14]([C:16]([O:18][CH2:19][CH:20]=[CH2:21])=[O:17])[C@H:13]([C:22](=[O:24])[NH:48][C:47]2[CH:46]=[CH:45][C:38]([C:39]([O:41][CH2:42][CH:43]=[CH2:44])=[O:40])=[CH:37][C:36]=2[O:35][CH2:32][CH:33]=[CH2:34])[CH2:12]1)(=[O:9])[CH3:8]

Participants

8

Reactant 4

HCID 79724-Methylmorpholine2×HCID 65578Oxalyl chlorideHCID 15299255(2S,4S)-4-Acetylthio-1-allyloxycarbonyl-2-carboxypyrrolidineHCID 19432469Allyl 3-allyloxy-4-aminobenzoate

Product 2

HCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 56974068(2S,4S)-4-acetylthio-1-allyloxycarbonyl-2-(4-allyloxycarbonyl-2-allyloxyphenylcarbamoyl)pyrrolidine

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

Vilsmeier reagent was prepared by treatment of DMF (0.56 ml, 7.2 mM) in dichloromethane (35 ml) under argon with oxalyl chloride (0.58 ml, 6.6 mM) at -10° for 30 minutes. The (2S,4S)-4-acetylthio-1-allyloxycarbonyl-2-carboxypyrrolidine was added to this in one portion, followed by N-methylmorpholine (0.87 ml, 7.9 mM) and stirring continued for 30 minutes at -10°. After cooling to -20°, allyl 3-allyloxy-4-aminobenzoate (1.54 g, 6.6 mM) plus N-methyl morpholine (0.87 ml, 7.9 mM) dissolved in dichloromethane (20 ml) were added dropwise. The temperature was allowed to rise to 5° and stirring continued for 2 hours. After dilution with dichloromethane, the mixture was washed with a 2M aqueous solution of hydrochloric acid, water and a saturated aqueous solution of sodium bicarbonate. It was dried over MgSO4 and the solvent evaporated. Crude material was purified by medium pressure chromatography using a gradient of diethyl ether (0 to 10%) in dichloromethane to give (2S,4S)-4-acetylthio-1-allyloxycarbonyl-2-(4-allyloxycarbonyl-2-allyloxyphenylcarbamoyl)pyrrolidine (2.7 g).

Workup

  1. temperatureAfter cooling to -20°
  2. additionwere added dropwise
  3. customto rise to 5°
  4. stirringstirring
  5. waitcontinued for 2 hours
  6. washAfter dilution with dichloromethane, the mixture was washed with a 2M aqueous solution of hydrochloric acid, water
  7. dry with materialIt was dried over MgSO4
  8. customthe solvent evaporated
  9. customCrude material was purified by medium pressure chromatography

Sources & evidence

ORD record
ord-34fbb43f2c664eda8175a78dc9e94f66
Source dataset
uspto-grants-1996_07
Patent number
US05541178

Reaction notes

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