Water → 3-[[4-(4-Cyanophenyl)phenoxy]methyl]-1-(4-methoxybenzoyl)pyrrolidine-3-carboxylic acid

HRID 2060228Notes

Reaction equation

HRID 2060228 reaction equation
C[Si](C)(C)[O-].[Na+].O.C([O:10][C:11]([C:13]1([CH2:28][O:29][C:30]2[CH:35]=[CH:34][C:33]([C:36]3[CH:41]=[CH:40][C:39]([C:42]#[N:43])=[CH:38][CH:37]=3)=[CH:32][CH:31]=2)[CH2:17][CH2:16][N:15]([C:18](=[O:27])[C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)[CH2:14]1)=[O:12])C>C(#N)C>[C:42]([C:39]1[CH:40]=[CH:41][C:36]([C:33]2[CH:32]=[CH:31][C:30]([O:29][CH2:28][C:13]3([C:11]([OH:12])=[O:10])[CH2:17][CH2:16][N:15]([C:18](=[O:27])[C:19]4[CH:20]=[CH:21][C:22]([O:25][CH3:26])=[CH:23][CH:24]=4)[CH2:14]3)=[CH:35][CH:34]=2)=[CH:37][CH:38]=1)#[N:43]

Participants

5

Reactant 3

HCID 962WaterHCID 23672319Sodium trimethylsilanolateHCID 593222123-(4'-Cyano-biphenyl-4-yloxymethyl)-1-(4-methoxy-benzoyl)-pyrrolidine-3-carboxylic acid ethyl ester

Product 1

HCID 462130693-[[4-(4-Cyanophenyl)phenoxy]methyl]-1-(4-methoxybenzoyl)pyrrolidine-3-carboxylic acidYield 55%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Sodium trimethyl silanolate (72.1 g) and water (7.72 mL, 428.6 mmol) were added to a stirred solution of 3-(4′-cyano-biphenyl-4-yloxymethyl)-1-(4-methoxy-benzoyl)-pyrrolidine-3-carboxylic acid ethyl ester (see Preparation 28) (207.7 g, 428.6 mmol) in acetonitrile (2090 mL). The resulting mixture was stirred at RT for 18 hours. The reaction mixture was filtered and the solid was partitioned between ethyl acetate (2000 mL) and aqueous hydrogen chloride solution (2000 mL, 2M). The organic layer was washed with water (1000 mL) then concentrated under reduced pressure to afford a pale orange foam. This was recrystallised twice, from ethyl acetate (700 mL) then isopropyl alcohol (700 mL) to afford the title compound as a white solid (107.2 g, 55%).

Workup

  1. filtrationThe reaction mixture was filtered
  2. customthe solid was partitioned between ethyl acetate (2000 mL) and aqueous hydrogen chloride solution (2000 mL, 2M)
  3. washThe organic layer was washed with water (1000 mL)
  4. concentrationthen concentrated under reduced pressure
  5. customto afford a pale orange foam
  6. customThis was recrystallised twice, from ethyl acetate (700 mL)

Sources & evidence

ORD record
ord-37f2a7039ba94bdab14ebec48f7d6cd0
Source dataset
uspto-grants-2012_10
Patent number
US08278343B2

Reaction notes

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