Water → ethyl 3-amino-5-{(3R)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}-1-(2-chlorobenzyl)-4-cyano-1H-pyrrole-2-carboxylate

HRID 1819301Notes

Reaction equation

HRID 1819301 reaction equation
[CH2:1]([O:3][C:4](=[O:35])[CH2:5][N:6]([C:15]([N:21]1[CH2:26][CH2:25][CH2:24][C@@H:23]([NH:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:22]1)=[C:16]([C:19]#[N:20])[C:17]#[N:18])[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[Cl:14])[CH3:2].[H-].[Na+].O>O1CCCC1>[NH2:18][C:17]1[C:16]([C:19]#[N:20])=[C:15]([N:21]2[CH2:26][CH2:25][CH2:24][C@@H:23]([NH:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:22]2)[N:6]([CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[Cl:14])[C:5]=1[C:4]([O:3][CH2:1][CH3:2])=[O:35]

Participants

5

Reactant 3

HCID 962WaterHCID 24758Sodium hydrideHCID 86625680N-(1-{(3R)-3-[(tert-Butoxycarbonyl)amino]-piperidin-1-yl}-2,2-dicyanovinyl)-N-(2-chlorobenzyl)glycine ethyl ester

Product 1

HCID 53309630ethyl 3-amino-5-{(3R)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}-1-(2-chlorobenzyl)-4-cyano-1H-pyrrole-2-carboxylateYield 93.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A solution of N-(1-{(3R)-3-[(tertbutoxycarbonyl)amino]piperidin-1-yl}-2,2-dicyanovinyl)-N-(2-chlorobenzyl)glycine ethyl ester (320 mg) in tetrahydrofuran (5 ml) was cooled to 0° C., followed by adding thereto sodium hydride (33 mg), and the resulting mixture was stirred for 1 hour while being warmed to 25° C. Water was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate and then filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (hexane/ethyl acetate=3/1 to 1/1) to obtain the title compound (300 mg).

Workup

  1. additionby adding
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer was washed with a saturated aqueous sodium chloride solution
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe resulting residue was purified by a silica gel column chromatography (hexane/ethyl acetate=3/1 to 1/1)

Sources & evidence

ORD record
ord-8608cc5016bc40818d44b41505865146
Source dataset
uspto-grants-2009_10
Patent number
US07601728B2

Reaction notes

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