4-Methylmorpholine → HCID 71245379, compound

HRID 1186003Notes

Reaction equation

HRID 1186003 reaction equation
[C:1]([O:4][CH2:5][C@H:6]([NH:17][C:18]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19])[C:7]([N:9]1[CH2:13][CH2:12][CH2:11][C@H:10]1[C:14](O)=[O:15])=[O:8])(=[O:3])[CH3:2].CN1CCOCC1.[OH:35][C@H:36]([CH3:50])[C@H:37]([NH:42][C:43]([C@@H:45]1[CH2:49][CH2:48][CH2:47][NH:46]1)=[O:44])[C:38]([O:40][CH3:41])=[O:39]>C(Cl)Cl.CN(C=O)C>[C:1]([O:4][CH2:5][C@@H:6]([NH:17][C:18]([O:20][CH2:21][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)=[O:19])[C:7]([N:9]1[CH2:13][CH2:12][CH2:11][C@H:10]1[C:14]([N:46]1[CH2:47][CH2:48][CH2:49][C@H:45]1[C:43]([NH:42][C@@H:37]([C@H:36]([OH:35])[CH3:50])[C:38]([O:40][CH3:41])=[O:39])=[O:44])=[O:15])=[O:8])(=[O:3])[CH3:2]

Participants

6

Reactant 3

HCID 79724-Methylmorpholine2×HCID 12693577HCID 12693577, compoundHCID 71245312HCID 71245312, compound

Product 1

HCID 71245379HCID 71245379, compoundYield 19%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

Compound 3 (1.0 g, 2.64 mmol) was dissolved in CH2Cl2 (10 mL), NMM (0.32 g, 3.17 mmol) and IBCF (0.41 g, 3.04 mmol) were added to the reaction mixture at −15° C. and stirred for minutes under inert atmosphere. A mixture of (2S,3R)-methyl 3-hydroxy-2-((S)-pyrrolidine-2-carboxamido)-butanoate (4) (0.73 g, 3.17 mmol) and NMM (0.35 mL) in DMF (3 mL) were added drop wise to the reaction mixture at −15° C. and stirring was continued for another 3 h at RT. The reaction mixture was diluted with DCM (200 mL), washed with water (20 mL), citric acid solution (2×20 mL) and brine (2×50 mL). The separated organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude residue obtained was purified by silica gel column chromatography eluting with 5% CH3OH/EtOAc to afford compound (5) (0.29 g, 19%).

Workup

  1. additionwere added drop wise to the reaction mixture at −15° C.
  2. stirringstirring
  3. washwashed with water (20 mL), citric acid solution (2×20 mL) and brine (2×50 mL)
  4. dry with materialThe separated organic layer was dried over anhydrous Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe crude residue obtained
  7. customwas purified by silica gel column chromatography
  8. washeluting with 5% CH3OH/EtOAc

Sources & evidence

ORD record
ord-cf166a21c09042a3ac85d98538d1e9f5
Source dataset
uspto-grants-2014_03
Patent number
US08673843B2

Reaction notes

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