4-Methylmorpholine → HCID 71245577, compound

HRID 1186001Notes

Reaction equation

HRID 1186001 reaction equation
[C:1]([O:4][CH2:5][C@H:6]([NH:10][C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])[C:7]([OH:9])=O)(=[O:3])[CH3:2].CN1CCOCC1.ClC(OCC(C)C)=O.[NH:36]1[CH2:40][CH2:39][CH2:38][C@H:37]1[C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42]>C(Cl)Cl.CN(C=O)C>[C:1]([O:4][CH2:5][C@H:6]([NH:10][C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])[C:7]([N:36]1[CH2:40][CH2:39][CH2:38][C@H:37]1[C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])=[O:9])(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 79724-Methylmorpholine2×HCID 62365Isobutyl chloroformateHCID 6453108L-Proline 1,1-dimethylethyl esterHCID 11196763HCID 11196763, compound

Product 1

HCID 71245577HCID 71245577, compoundYield 69.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

(S)-3-Acetoxy-2-(benzyloxycarbonylamino)-propanoic acid (1.5 g, 5.33 mmol) was dissolved in CH2Cl2 (15 mL). N-Methylmorpholine (NMM) (0.64 mL, 5.87 mmol) and isobutyl chloroformate (IBCF) (0.72 mL, 6.12 mmol) were added at −15° C. and stirred for 30 minutes under inert atmosphere. A mixture of (S)-tert-butyl pyrrolidine-2-carboxylate (1) (998 mg, 5.87 mmol) and NMM (0.64 mL, 5.87 mmol) in DMF (5 mL) were added drop wise to the reaction mixture and stirring was continued for another 3 h at RT. The reaction mixture was diluted with DCM (200 mL), washed with water (50 mL), citric acid solution (10 mL) and brine (10 mL). The separated organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The obtained crude residue was purified by silica gel column chromatography eluting with 30% EtOAc/Hexane to afford compound 2 (1.6 g, 69.5%).

Workup

  1. additionwere added drop wise to the reaction mixture
  2. stirringstirring
  3. waitwas continued for another 3 h at RT
  4. washwashed with water (50 mL), citric acid solution (10 mL) and brine (10 mL)
  5. dry with materialThe separated organic layer was dried over anhydrous Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe obtained crude residue
  8. customwas purified by silica gel column chromatography
  9. washeluting with 30% EtOAc/Hexane

Sources & evidence

ORD record
ord-eaf3e8757e6b4e42bb6f776c31968d72
Source dataset
uspto-grants-2014_03
Patent number
US08673843B2

Reaction notes

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