4-Methylmorpholine → 2-[(2S,4EZ)-1-(biphenyl-4-ylcarbonyl)-4-(methoxyimino) pyrrolidin-2-yl]-N-[(2S)-2-hydroxy-2-phenylethyl] acetamide

HRID 225966Notes

Reaction equation

HRID 225966 reaction equation
[C:1]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:6]=[CH:5][C:4]([C:7]([N:9]2[CH2:13][C:12](=[N:14][O:15][CH3:16])[CH2:11][C@H:10]2[CH2:17][C:18](O)=[O:19])=[O:8])=[CH:3][CH:2]=1.CN1CCOCC1.ClC(OCC(C)C)=O.[NH2:42][CH2:43][C@H:44]([C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)[OH:45]>O1CCCC1.ClCCl>[C:1]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:6]=[CH:5][C:4]([C:7]([N:9]2[CH2:13][C:12](=[N:14][O:15][CH3:16])[CH2:11][C@H:10]2[CH2:17][C:18]([NH:42][CH2:43][C@@H:44]([OH:45])[C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)=[O:19])=[O:8])=[CH:3][CH:2]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 643217(1S)-2-amino-1-phenylethan-1-olHCID 131727525[(2S,4EZ)-1-(biphenyl-4-ylcarbonyl)-4-(methoxyimino)pyrrolidin-2-yl] acetic acid2×

Product 1

HCID 1317275292-[(2S,4EZ)-1-(biphenyl-4-ylcarbonyl)-4-(methoxyimino) pyrrolidin-2-yl]-N-[(2S)-2-hydroxy-2-phenylethyl] acetamideYield 106%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of [(2S,4EZ)-1-(biphenyl-4-ylcarbonyl)-4-(methoxyimino)pyrrolidin-2-yl]acetic acid (Intermediate 7, 25 mg, 0.07 mmol) in tetrahydrofuran (1 ml) at −25° C. were added NMM (18 mg, 0.18 mmol) followed by isobutyl chloroformate (10 mg, 0.07 mmol). The reaction mixture was stirred 10 min then a solution of (S)-2-amino-1-phenylethanol (10 mg, 0.07 mmol) in tetrahydrofuran (1 ml). The reaction was allowed to warm up to room temperature and was stirred overnight. Dichloromethane was added and the organic phase was washed with NH4Cl, NaHCO3 then brine. The organic phase was dried (MgSO4) and concentrated to afford 2-[(2S,4EZ)-1-(biphenyl-4-ylcarbonyl)-4-(methoxyimino) pyrrolidin-2-yl]-N-[(2S)-2-hydroxy-2-phenylethyl]acetamide (35 mg). Yield: 94%. HPLC purity: 90%

Workup

  1. stirringwas stirred overnight
  2. washthe organic phase was washed with NH4Cl, NaHCO3
  3. dry with materialThe organic phase was dried (MgSO4)
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-bc09de433a64446ab7b240d42566f2df
Source dataset
uspto-grants-2009_07
Patent number
US07557136B2

Reaction notes

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