Acetic Acid → (3S)-2-[(2R)-2-({formyl[(phenylmethyl)oxy]amino}methyl)heptanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acid

HRID 1396941Notes

Reaction equation

HRID 1396941 reaction equation
[C:1]1([CH2:7][O:8][C:9]([N:11]2[CH2:15][CH2:14][CH:13]([C:16]([OH:18])=[O:17])[NH:12]2)=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CCN(C(C)C)C(C)C.[CH:28]([N:30]([CH2:39][C@@H:40]([CH2:44][CH2:45][CH2:46][CH2:47][CH3:48])[C:41](F)=[O:42])[O:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)=[O:29].CC(O)=O>CN(C=O)C>[CH:28]([N:30]([CH2:39][C@@H:40]([CH2:44][CH2:45][CH2:46][CH2:47][CH3:48])[C:41]([N:12]1[C@H:13]([C:16]([OH:18])=[O:17])[CH2:14][CH2:15][N:11]1[C:9]([O:8][CH2:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)=[O:10])=[O:42])[O:31][CH2:32][C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1)=[O:29]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 81531Diisopropylethylamine2×HCID 537448401-(Benzyloxy carbonyl)pyrazolidine-3-carboxylic acidHCID 86706374(2R)-2-({formyl[(phenylmethyl)oxy]amino}methyl)heptanoyl fluoride

Product 1

HCID 86706375(3S)-2-[(2R)-2-({formyl[(phenylmethyl)oxy]amino}methyl)heptanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acidYield 35%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a 50 mL round-bottomed flask was added 1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acid (3.00 g, 8.23 mmol) and Hunig's base (DIPEA) (4.41 mL, 25.3 mmol) in DMF (15 mL). To this mixture was added (2R)-2-({formyl[(phenylmethyl)oxy]amino}methyl)heptanoyl fluoride (1.87 g, 6.33 mmol) in DMF (5 mL) dropwise. The reaction mixture was stirred at room temperature overnight, then was stored in refrigerator for two days. HOAc (3 ml) was added to neutralize the excess Hunig's base. The resulting solution was purified by RP-HPLC to provide (3S)-2-[(2R)-2-({formyl[(phenylmethyl)oxy]amino}methyl)heptanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acid as a white solid (1.153 g, 35%). LCMS: (M+H)+: 526.0.

Workup

  1. waitwas stored in refrigerator for two days
  2. customThe resulting solution was purified by RP-HPLC

Sources & evidence

ORD record
ord-3b94aaab4b05410995e60305efdb0c87
Source dataset
uspto-grants-2014_12
Patent number
US08901119B2

Reaction notes

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