4-Methylmorpholine → HCID 71245299, compound

HRID 1186012Notes

Reaction equation

HRID 1186012 reaction equation
C([O:4][CH2:5][C@@H:6]([NH:32][C:33]([O:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)=[O:34])[C:7]([N:9]1[CH2:13][CH2:12][CH2:11][C@H:10]1[C:14]([N:16]1[CH2:20][CH2:19][CH2:18][C@H:17]1[C:21]([NH:23][C@@H:24]([C@H:29]([OH:31])C)[C:25]([O:27][CH3:28])=[O:26])=[O:22])=[O:15])=[O:8])(=O)C.CN1CCOCC1>C(Cl)Cl.CN(C=O)C>[CH2:36]([O:35][C:33]([NH:32][C@@H:6]([CH2:5][OH:4])[C:7]([N:9]1[CH2:13][CH2:12][CH2:11][C@H:10]1[C:14]([N:16]1[CH2:20][CH2:19][CH2:18][C@H:17]1[C:21]([NH:23][C@@H:24]([CH2:29][OH:31])[C:25]([O:27][CH3:28])=[O:26])=[O:22])=[O:15])=[O:8])=[O:34])[C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1

Participants

5

Reactant 2

HCID 79724-Methylmorpholine2×HCID 71245379HCID 71245379, compound

Product 1

HCID 71245299HCID 71245299, compoundYield 14.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

(S)-1-((S)-3-Acetoxy-2-(benzyloxycarbonylamino)-propanoyl)-pyrrolidine-2-carboxylic acid (5) (400 mg, 1.05 mmol) was dissolved in CH2Cl2 (2 mL), NMM (0.13 mL) and IBCF (0.14 mL) were added at −15° C. and stirred for 30 minutes under inert atmosphere. A mixture of(S)-methyl-3-hydroxy-2-((S)-pyrrolidine-2-carboxamido)-propanoate hydrochloride (4) (293 mg, 1.16 mmol) and NMM (0.13 mL) in DMF (2 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 (20 mL) and brine (10 mL). The separated organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The obtained crude material was purified by silica gel column chromatography eluting with 5% CH3OH/CH2Cl2 to afford compound 6 (80 mg, 13%).

Workup

  1. stirringstirring
  2. waitwas continued for another 3 h at RT
  3. washwashed with water (20 mL) and brine (10 mL)
  4. dry with materialThe separated organic layer was dried over anhydrous Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe obtained crude material
  7. customwas purified by silica gel column chromatography
  8. washeluting with 5% CH3OH/CH2Cl2

Sources & evidence

ORD record
ord-19700766d3ba4987aacf703fdf7bedeb
Source dataset
uspto-grants-2014_03
Patent number
US08673843B2

Reaction notes

Loading…