4-Methylmorpholine → HCID 71245451, compound

HRID 1186009Notes

Reaction equation

HRID 1186009 reaction equation
[C:1]([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:3])[CH3:2].[CH3:43]N1CCOCC1.OC[C@H](NC([C@@H]1CCCN1)=O)C(OC)=O>C(Cl)Cl.CN(C=O)C>[C:1]([O:4][C@@H:5]([CH3:43])[C@@H:6]([NH:32][C:33]([O:35][CH2:36][C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=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]([CH2:29][OH:31])[C:25]([O:27][CH3:28])=[O:26])=[O:22])=[O:15])=[O:8])(=[O:3])[CH3:2]

Participants

6

Reactant 3

HCID 79724-Methylmorpholine2×HCID 54033258HCID 54033258, compoundHCID 71245379HCID 71245379, compound

Product 1

HCID 71245451HCID 71245451, compoundYield 17.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

(2S)-1-((2R)-3-acetoxy-2-(benzyloxycarbonylamino)-butanoyl)-pyrrolidine-2-carboxylic acid (5) (1.3 g, 2.62 mmol) was dissolved in CH2Cl2 (15 mL), NMM (0.43 mL) and IBCF (0.51 mL) was added at −10° C. and stirred for 30 minutes under inert atmosphere. A mixture of(S)-methyl-3-hydroxy-2-((S)-pyrrolidine-2-carboxamido)-propionate (4) (992 mg, 3.93 mmol) and NMM (0.43 mL) 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 (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 obtained crude material was purified by silica gel column chromatography eluting with 5% CH3OH/CH2Cl2 to afford compound 6 (270 mg, 17.5%).

Workup

  1. stirringstirring
  2. waitwas continued for another 3 h at RT
  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 obtained crude material
  7. customwas purified by silica gel column chromatography
  8. washeluting with 5% CH3OH/CH2Cl2

Sources & evidence

ORD record
ord-941a27e6a157495ebf21357437c742c5
Source dataset
uspto-grants-2014_03
Patent number
US08673843B2

Reaction notes

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