Methyl bromoacetate → [[4-(5-Fluoro-2-methoxy-phenyl)-pyridin-3-yl]-(3-methanesulfonyl-5-trifluoromethyl-benzoyl)-amino]-acetic acid methyl ester

HRID 878337Notes

Reaction equation

HRID 878337 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:31][CH3:32])=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[NH:14][C:15](=[O:30])[C:16]2[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[C:18]([S:26]([CH3:29])(=[O:28])=[O:27])[CH:17]=2)[CH:7]=1.CC(C)([O-])C.[K+].Br[CH2:40][C:41]([O:43][CH3:44])=[O:42]>C1COCC1>[CH3:44][O:43][C:41](=[O:42])[CH2:40][N:14]([C:9]1[CH:10]=[N:11][CH:12]=[CH:13][C:8]=1[C:6]1[CH:7]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=1[O:31][CH3:32])[C:15](=[O:30])[C:16]1[CH:21]=[C:20]([C:22]([F:25])([F:23])[F:24])[CH:19]=[C:18]([S:26]([CH3:29])(=[O:28])=[O:27])[CH:17]=1

Participants

5

Reactant 3

HCID 60984Methyl bromoacetateHCID 23665647Potassium tert-butoxideHCID 70663253N-[4-(5-fluoro-2-methoxy-phenyl)-pyridin-3-yl]-3-methanesulfonyl-5-trifluoromethyl-benzamide

Product 1

HCID 70663372[[4-(5-Fluoro-2-methoxy-phenyl)-pyridin-3-yl]-(3-methanesulfonyl-5-trifluoromethyl-benzoyl)-amino]-acetic acid methyl esterYield 14%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of N-[4-(5-fluoro-2-methoxy-phenyl)-pyridin-3-yl]-3-methanesulfonyl-5-trifluoromethyl-benzamide (50 mg, 0.11 mmol) in THF (5 mL) were added potassium tert-butoxide (24 mg, 0.21 mmol) and methyl bromoacetate (22 mg, 0.14 mmol) at 0° C. and the reaction mixture was stirred for 12 hours at 25° C. The reaction mixture was quenched with water (5 mL) and extracted by EtOAc (2×20 mL). The combined EtOAc layers were dried over Na2SO4 and evaporated. The crude product was purified by preparative HPLC (ammonium acetate/acetonitrile) to get the desired compound as an off-white solid (8 mg, 14%). MS (ESI): m/z=541.0 [M+H]+.

Workup

  1. customThe reaction mixture was quenched with water (5 mL)
  2. extractionextracted by EtOAc (2×20 mL)
  3. dry with materialThe combined EtOAc layers were dried over Na2SO4
  4. customevaporated
  5. customThe crude product was purified by preparative HPLC (ammonium acetate/acetonitrile)

Sources & evidence

ORD record
ord-97afdf9954de4bbdab5d7cc84907eecc
Source dataset
uspto-grants-2015_03
Patent number
US08987307B2

Reaction notes

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