Tetrahydrofuran → N-[4-Amino-2-fluoro-3-(2-hydroxyethyl)phenyl]-2,2-difluoro-2-(4-fluoronaphthyl)acetamide

HRID 2184203Notes

Reaction equation

HRID 2184203 reaction equation
C([O:4][CH2:5][CH2:6][C:7]1[C:12]([F:13])=[C:11]([NH:14][C:15](=[O:30])[C:16]([F:29])([F:28])[C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:20]([F:27])=[CH:19][CH:18]=2)[CH:10]=[CH:9][C:8]=1[NH2:31])(=O)C.C1COCC1.C([O-])([O-])=O.[K+].[K+]>CO.O>[NH2:31][C:8]1[CH:9]=[CH:10][C:11]([NH:14][C:15](=[O:30])[C:16]([F:29])([F:28])[C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:20]([F:27])=[CH:19][CH:18]=2)=[C:12]([F:13])[C:7]=1[CH2:6][CH2:5][OH:4]

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 224753342-[2-Amino-5-[2,2-difluoro-2-(4-fluoronaphthyl)acetylamino]-6-fluorophenyl}ethyl Acetate

Product 1

HCID 20792218N-[4-Amino-2-fluoro-3-(2-hydroxyethyl)phenyl]-2,2-difluoro-2-(4-fluoronaphthyl)acetamideYield 96%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Procedure

To a solution of 2-{2-amino-5-[2,2-difluoro-2-(4-fluoronaphthyl)acetylamino]-6-fluorophenyl}ethyl acetate (3.8 g, 8.8 mmol), as prepared in the preceding step, in MeOH (40 mL) and THF (20 mL) was added a solution of K2CO3 (1.68 g, 12 mmol) in water (30 mL). The mixture was stirred at room temperature for 3 hours. Additional water (50 mL) was added, and the resulting mixture was extracted with EtOAc (3×50 mL). The extracts were combined, washed with brine, dried over Na2SO4, and concentrated in vacuo to give the title compound (3.3 g, 96%) as an off white solid. 1H-NMR (400 MHz, CDCl3) δ 8.27 (d, J=8.4 Hz, 1H), 8.19 (d, J=8.2 Hz, 1H), 8.13 (s, 1H), 7.81 (m, 2H), 7.64 (m, 2H), 7.19 (t, J=8.7 Hz, 1H), 6.47 (d, J=8.7 Hz, 1H), 4.07 (s, 2H), 3.89 (t, J=5.6 Hz, 2H), 2.85 (t, J=5.5 Hz, 2H).

Workup

  1. extractionthe resulting mixture was extracted with EtOAc (3×50 mL)
  2. washwashed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e0c665759b7b465fb5a18ebdf03ab2f0
Source dataset
uspto-grants-2005_05
Patent number
US06900231B2

Reaction notes

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