Potassium Carbonate → tert-Butyl 2-(4-(4-(4-chlorophenethylcarbamoyl)phenoxy)-3-cyanophenyl)acetate

HRID 453536Notes

Reaction equation

HRID 453536 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH2:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH:6]=[CH:7][C:8]=1F)#[N:2].[Cl:18][C:19]1[CH:36]=[CH:35][C:22]([CH2:23][CH2:24][NH:25][C:26](=[O:34])[C:27]2[CH:32]=[CH:31][C:30]([OH:33])=[CH:29][CH:28]=2)=[CH:21][CH:20]=1.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.C(OCC)(=O)C>[Cl:18][C:19]1[CH:20]=[CH:21][C:22]([CH2:23][CH2:24][NH:25][C:26]([C:27]2[CH:32]=[CH:31][C:30]([O:33][C:8]3[CH:7]=[CH:6][C:5]([CH2:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[CH:4][C:3]=3[C:1]#[N:2])=[CH:29][CH:28]=2)=[O:34])=[CH:35][CH:36]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 45925946HCID 45925946, compoundHCID 60628097N-(4-chlorophenethyl)-4-hydroxybenzamide

Product 1

HCID 68467179tert-Butyl 2-(4-(4-(4-chlorophenethylcarbamoyl)phenoxy)-3-cyanophenyl)acetateYield 40%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of tert-butyl 2-(3-cyano-4-fluorophenyl)acetate (1.32 g, 5.59 mmol), N-(4-chlorophenethyl)-4-hydroxybenzamide (1.85 g, 671 mmol), and potassium carbonate (0.93 g, 6.70 mmol) in DMSO (10 ml) was stirred at 90° C. for 1 day. The reaction was cooled, diluted with ethyl acetate, and washed with 10% aqueous Na2CO3. The aqueous layer was back extracted with ethyl acetate. The organic washes were combined, washed with 10% Na2CO3 and brine, dried over sodium sulfate and concentrated. The crude material was purified by silica gel chromatography, eluting with a gradient of 5% ethyl acetate/hexanes to 60% ethyl acetate/hexanes gave tert-butyl 2-(4-(4-((4-chlorophenethyl)carbamoyl)phenoxy)-3-cyanophenyl)acetate (1.09 g, 40%).

Workup

  1. temperatureThe reaction was cooled
  2. washwashed with 10% aqueous Na2CO3
  3. extractionThe aqueous layer was back extracted with ethyl acetate
  4. washwashed with 10% Na2CO3 and brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customThe crude material was purified by silica gel chromatography
  8. washeluting with a gradient of 5% ethyl acetate/hexanes to 60% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-49a01a6ed93c4c6d8fca67880f261b1a
Source dataset
uspto-grants-2013_07
Patent number
US08492437B2

Reaction notes

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