Acetohydrazide → (S)-tert-butyl 4-(3-(4-(2-acetylhydrazinecarbonyl)-2-fluorophenoxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate

HRID 407955Notes

Reaction equation

HRID 407955 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH2:18][CH2:17][C@H:16]([O:19][C:20]3[CH:28]=[CH:27][C:23]([C:24]([OH:26])=O)=[CH:22][C:21]=3[F:29])[C:15]2=[O:30])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:31]([NH:34][NH2:35])(=[O:33])[CH3:32].C(N(C(C)C)C(C)C)C.O=C1N(P(Cl)(N2CCOC2=O)=O)CCO1>C(Cl)Cl.O>[C:31]([NH:34][NH:35][C:24]([C:23]1[CH:27]=[CH:28][C:20]([O:19][C@H:16]2[CH2:17][CH2:18][N:14]([CH:11]3[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:13][CH2:12]3)[C:15]2=[O:30])=[C:21]([F:29])[CH:22]=1)=[O:26])(=[O:33])[CH3:32]

Participants

7

Reactant 4

HCID 14039AcetohydrazideHCID 81531DiisopropylethylamineHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 67469693(S)-4-(1-(1-(tert-butoxycarbonyl)piperidin-4-yl)-2-oxopyrrolidin-3-yloxy)-3-fluorobenzoic acid

Product 1

HCID 86688103(S)-tert-butyl 4-(3-(4-(2-acetylhydrazinecarbonyl)-2-fluorophenoxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylateYield 102%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

(S)-4-(1-(1-(tert-butoxycarbonyl)piperidin-4-yl)-2-oxopyrrolidin-3-yloxy)-3-fluorobenzoic acid (834 mg, 1.97 mmol), acetohydrazide (219 mg, 2.96 mmol) and N-ethyl-N-isopropylpropan-2-amine (1375 μL, 7.90 mmol) were dissolved in CH2Cl2 (20 mL) and bis(2-oxooxazolidin-3-yl)phosphinic chloride (2010 mg, 7.90 mmol) was added and stirred at ambient temperature for 3 hours. The reaction was poured into water, extracted with EtOAc, washed with brine, dried over Na2SO4, filtered and concentrated to afford crude (S)-tert-butyl 4-(3-(4-(2-acetylhydrazinecarbonyl)-2-fluorophenoxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate (960 mg, 2.01 mmol, 102% yield) which was taken forward without further purification.

Workup

  1. extractionextracted with EtOAc
  2. washwashed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-8036d1d8d0ee4e1ab1de5c9082012e86
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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