Diisopropylethylamine → (3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acid

HRID 1396910Notes

Reaction equation

HRID 1396910 reaction equation
[CH:1]1([CH2:6][C@H:7]([CH2:11][N:12]([CH:21]=[O:22])[O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:8](F)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:23]([O:30][C:31]([N:33]1[CH2:37][CH2:36][CH:35]([C:38]([OH:40])=[O:39])[NH:34]1)=[O:32])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.CCN(C(C)C)C(C)C>CN(C=O)C.C(OCC)(=O)C>[CH:1]1([CH2:6][C@H:7]([CH2:11][N:12]([CH:21]=[O:22])[O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:8]([N:34]2[C@H:35]([C:38]([OH:40])=[O:39])[CH2:36][CH2:37][N:33]2[C:31]([O:30][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:32])=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 537448401-(Benzyloxy carbonyl)pyrazolidine-3-carboxylic acidHCID 86706340(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl fluoride

Product 1

HCID 86706346(3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acidYield 14.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

(2R)-3-Cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl fluoride (11.37 g, 37 mmol) in 50 mL of DMF was added into the solution of 1-(benzyloxy carbonyl)pyrazolidine-3-carboxylic acid (12.04 g, 48.1 mmol) and Hunig's base (25.8 ml, 148 mmol) in 70 ml of DMF. The reaction was stirred at 25° C. for 5 hrs. The reaction was diluted with ethyl acetate, and the resulting solution was washed with aqueous NH4Cl (2×200 ml). The aqueous solution was extracted with ethyl acetate (5×100 ml). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated to give a residue. The residue was purified by silica Gel chromatography and then recrystallization from ethyl acetate and hexane to yield (3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acid (2.834 g, 5.27 mmol, 14% yield). MS (ES+) m/z 538.1 (MH+).

Workup

  1. washthe resulting solution was washed with aqueous NH4Cl (2×200 ml)
  2. extractionThe aqueous solution was extracted with ethyl acetate (5×100 ml)
  3. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a residue
  7. customThe residue was purified by silica Gel chromatography
  8. customrecrystallization from ethyl acetate and hexane

Sources & evidence

ORD record
ord-c6c3442ea92a469aa79d1ed6634cbf02
Source dataset
uspto-grants-2014_12
Patent number
US08901119B2

Reaction notes

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