4-Methylmorpholine → HCID 71245360, compound

HRID 1186023Notes

Reaction equation

HRID 1186023 reaction equation
[C:1]([O:4][C@H:5]([CH3:18])[C@H:6]([NH:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[C:7]([OH:9])=O)(=[O:3])[CH3:2].CN1CCOCC1.[C:26]([O:29][C@H:30]([CH3:58])[C@H:31]([NH:36][C:37]([C:39]1([CH2:51][C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)[CH2:43][CH2:42][CH2:41][N:40]1[C:44]([C@@H:46]1[CH2:50][CH2:49][CH2:48][NH:47]1)=[O:45])=[O:38])[C:32]([O:34][CH3:35])=[O:33])(=[O:28])[CH3:27]>C(Cl)Cl.CN(C=O)C>[CH3:35][O:34][C:32](=[O:33])[C@@H:31]([NH:36][C:37]([C:39]1([CH2:51][C:52]2[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=2)[CH2:43][CH2:42][CH2:41][N:40]1[C:44]([C@@H:46]1[CH2:50][CH2:49][CH2:48][N:47]1[C:7](=[O:9])[C@@H:6]([NH:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[C@H:5]([O:4][C:1](=[O:3])[CH3:2])[CH3:18])=[O:45])=[O:38])[C@H:30]([O:29][C:26](=[O:28])[CH3:27])[CH3:58]

Participants

6

Reactant 3

HCID 79724-MethylmorpholineHCID 71245274HCID 71245274, compoundHCID 73553823HCID 73553823, compound

Product 1

HCID 71245360HCID 71245360, compoundYield 20%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of compound (2S,3R)-3-acetoxy-2-(tert-butoxycarbonylamino)-butanoic acid 12 (199 mg, 0.76 mmol) in CH2Cl2 (6 mL) was under inert atmosphere were added IBCF (125 mg, 0.91 mmol) and NMM (154 mg, 1.52 mmol) at −15° C. and stirred for 1 h. A solution of (2S,3R)-methyl 3-acetoxy-2-(2-benzyl-1-((S)-pyrrolidine-2-carbonyl)pyrrolidine-2-carboxamido)-butanoate 8 (350 mg, 0.76 mmol) in DMF (2 mL) was added to the reaction mixture and stirred for 1 h at −15° C. The resultant reaction mixture was allowed to warm to RT and stirred for 19 h. The reaction mixture was extracted with EtOAc and the separated organic layer was washed with water (20 mL), followed by brine (20 mL), dried over Na2SO4 and concentrated under reduced pressure. The crude material was purified by preparative HPLC to afford compound 13 (100 mg, 20%).

Workup

  1. stirringstirred for 1 h at −15° C
  2. customThe resultant reaction mixture
  3. stirringstirred for 19 h
  4. extractionThe reaction mixture was extracted with EtOAc
  5. washthe separated organic layer was washed with water (20 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customThe crude material was purified by preparative HPLC

Sources & evidence

ORD record
ord-80f4abd698054236ae95cce865e45852
Source dataset
uspto-grants-2014_03
Patent number
US08673843B2

Reaction notes

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