4-Methylmorpholine → HCID 86584830, compound

HRID 1264379Notes

Reaction equation

HRID 1264379 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([S:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2)[CH2:10][C@H:9]1[C:23]([OH:25])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.OC1C2N=NNC=2C=CC=1.CCN=C=NCCCN(C)C.Cl.[CH3:55][NH:56][O:57][CH3:58]>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([S:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2)[CH2:10][C@H:9]1[C:23](=[O:25])[N:56]([O:57][CH3:58])[CH3:55])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 69429791HCID 69429791, compoundHCID 178418300HCID 178418300, compound

Product 1

HCID 86584830HCID 86584830, compoundYield 62.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

30 g (81.6 mmol) (2S,4R)-4-(4-Methoxy-benzylsulfanyl)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester in 800 ml CH2Cl2 were treated with 62.8 ml (571.2, 7 eq) NMM, 2.19 g (16.24 mmol, 0.2 eq) hydroxybenzotriazole, 37.5 g (195.84 mmol, 2.4 eq) EDCI and 17.5 g (179.52 mmol, 2.2 eq) N,O-dimethylhydroxylamine-hydrochloride. The solution was stirred for 3 h at RT, concentrated and dissolved in 500 ml 1M KHSO4 solution and 500 ml EtOAc were added. The organic layer was separated and washed with brine, dried over Na2SO4 and evaporated. The crude product was purified by flash chromatography on silica gel with EtOAc:hexane 1:1 as eluent yielding 3.6 g (62.4%) (2S,4R)-4-(4-Methoxy-benzylsulfanyl)-2-(methoxy-methyl-carbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester as light yellow oil, MS: 411 (MH+).

Workup

  1. concentrationconcentrated
  2. dissolutiondissolved in 500 ml 1M KHSO4 solution
  3. addition500 ml EtOAc were added
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried over Na2SO4
  7. customevaporated
  8. customThe crude product was purified by flash chromatography on silica gel with EtOAc:hexane 1:1 as eluent

Sources & evidence

ORD record
ord-8eae0e70efd642aa8630cea20b3ceb66
Source dataset
uspto-grants-2003_04
Patent number
US06541638B2

Reaction notes

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