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

HRID 228176Notes

Reaction equation

HRID 228176 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-57738adc31ae4a3bbd3ed8c6a183557f
Source dataset
uspto-grants-2009_07
Patent number
US07560463B2

Reaction notes

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