Water → Benzyl-{2-[4-(3-chloro-4-cyano-phenoxy)-phenyl]-ethyl}-carbamic acid tert-butyl ester

HRID 492332Notes

Reaction equation

HRID 492332 reaction equation
[C:1]([O:5][C:6](=[O:24])[N:7]([CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[K+].[K+].[Cl:31][C:32]1[CH:39]=[C:38](F)[CH:37]=[CH:36][C:33]=1[C:34]#[N:35].O>CN(C=O)C>[C:1]([O:5][C:6](=[O:24])[N:7]([CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:38]2[CH:37]=[CH:36][C:33]([C:34]#[N:35])=[C:32]([Cl:31])[CH:39]=2)=[CH:12][CH:11]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 1090002-Chloro-4-fluorobenzonitrileHCID 59717863HCID 59717863, compound

Product 1

HCID 59729914Benzyl-{2-[4-(3-chloro-4-cyano-phenoxy)-phenyl]-ethyl}-carbamic acid tert-butyl esterYield 95.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Combine the compound from Example 218 step 2 (692 mg, 2.12 mmol) and K2CO3 (323 mg, 2.33 mmol) in DMF (9 mL), stir the mixture at room temperature for 30 min and then add 2-chloro-4-fluoro-benzonitrile (330 mg, 2.12 mmol), and heat at 100° C. overnight. Cool to ambient temperature and pour into water. Extract the aqueous layer with EtOAc. Dry the organic layer over Na2SO4 and eliminate the solvent. Purify by flash chromatography on silica gel (eluent: EtOAc/hexane 15/85) to obtain the title compound (940 mg, 95%). Electrospray MS M−1 ion=461, 1H-NMR (CDCl3, 400 MHz): 7.57 (d, 1H, J=7.8 Hz), 7.36-7.13 (m, 7H), 7.00-6.85 (m, 4H), 4.44-4.36 (m, 2H), 3.49-3.32 (m, 2H), 2.83-2.73 (m, 2H), 1.51-1.43 (m, 9H).

Workup

  1. extractionExtract the aqueous layer with EtOAc
  2. dry with materialDry the organic layer over Na2SO4
  3. customPurify by flash chromatography on silica gel (eluent: EtOAc/hexane 15/85)

Sources & evidence

ORD record
ord-063faae5bfae4968a6fdb8d2041bd08f
Source dataset
uspto-grants-2009_05
Patent number
US07531557B2

Reaction notes

Loading…