Potassium Carbonate → Tert-butyl 2-(3-cyano-4-(4-(3,4-dichlorobenzamido)phenoxy)phenyl)propanoate

HRID 1927733Notes

Reaction equation

HRID 1927733 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:10]([CH3:18])[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH:6]=[CH:7][C:8]=1F)#[N:2].[Cl:19][C:20]1[CH:21]=[C:22]([CH:33]=[CH:34][C:35]=1[Cl:36])[C:23]([NH:25][C:26]1[CH:31]=[CH:30][C:29]([OH:32])=[CH:28][CH:27]=1)=[O:24].C([O-])([O-])=O.[K+].[K+]>CS(C)=O.CCOC(C)=O.C(=O)([O-])[O-].[Na+].[Na+]>[C:1]([C:3]1[CH:4]=[C:5]([CH:10]([CH3:18])[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH:6]=[CH:7][C:8]=1[O:32][C:29]1[CH:30]=[CH:31][C:26]([NH:25][C:23](=[O:24])[C:22]2[CH:33]=[CH:34][C:35]([Cl:36])=[C:20]([Cl:19])[CH:21]=2)=[CH:27][CH:28]=1)#[N:2]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 9768083,4-dichloro-N-(4-hydroxyphenyl)benzamideHCID 68467119Tert-butyl 2-(3-cyano-4-fluorophenyl)propanoate

Product 1

HCID 68466209Tert-butyl 2-(3-cyano-4-(4-(3,4-dichlorobenzamido)phenoxy)phenyl)propanoateYield 55.3%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
125 °C

Procedure

To a stirred solution of tert-butyl 2-(3-cyano-4-fluorophenyl)propanoate (360 mg, 1.44 mmol) from Step A and 3,4-dichloro-N-(4-hydroxyphenyl)benzamide (488 mg, 1.73 mmol) from Step B in DMSO (4 ml) was added K2CO3 (240 mg, 1.73 mmol). The reaction was stirred 125° C. overnight, then cooled to ambient temperature and diluted with EtOAc and 10% aqueous sodium carbonate. The aqueous phase was extracted with EtOAc and the combined organics washed with 10% aqueous sodium carbonate and brine, dried over MgSO4, concentrated and purified on a Biotage Horizon (40+M 5% to 50% B:EtOAc, 21 ml-1008 ml). The appropriate fractions were then combined and concentrated to give tert-butyl 2-(3-cyano-4-(4-(3,4-dichlorobenzamido)phenoxy)phenyl)propanoate (0.476 g, 0.797 mmol, 55%). 1H NMR (400 MHz, CDCl3) δ 7.99 (s, 1H), 7.84 (bs, N—H), 7.72 (d, J=9.3 Hz, 1H), 7.67 (d, J=8.7 Hz, 2H), 7.60 (m, 2H), 7.42 (d, J=8.6 Hz, 1H), 7.11 (d, J=7.7, 2H), 6.83 (d, J=8.7 Hz, 1H), 3.61 (q, J=7.1 Hz, 1H), 1.45 (d, J=7.5 Hz, 3H), 1.42 (s, 9H).

Workup

  1. temperaturecooled to ambient temperature
  2. extractionThe aqueous phase was extracted with EtOAc
  3. washthe combined organics washed with 10% aqueous sodium carbonate and brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. custompurified on a Biotage Horizon (40+M 5% to 50% B:EtOAc, 21 ml-1008 ml)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-223e60ba5db44069814f95cda433b9ff
Source dataset
uspto-grants-2012_05
Patent number
US08183289B2

Reaction notes

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