Sodium borohydride → 3,4-Difluoro-2-[2-fluoro-4-(hydroxymethyl)anilino]-N-(2-hydroxyethoxy)benzamide

HRID 2181458Notes

Reaction equation

HRID 2181458 reaction equation
[F:1][C:2]1[C:3]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([CH:23]=C)=[CH:19][C:18]=2[F:25])=[C:4]([CH:12]=[CH:13][C:14]=1[F:15])[C:5]([NH:7][O:8][CH2:9][CH2:10][OH:11])=[O:6].CC(C)=[O:28].C(=O)=O.[BH4-].[Na+]>CO>[F:1][C:2]1[C:3]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([CH2:23][OH:28])=[CH:19][C:18]=2[F:25])=[C:4]([CH:12]=[CH:13][C:14]=1[F:15])[C:5]([NH:7][O:8][CH2:9][CH2:10][OH:11])=[O:6]

Participants

5

Reactant 3

HCID 4311764Sodium borohydrideHCID 102369933,4-Difluoro-2-(2-fluoro-4-vinylanilino)-N-(2-hydroxyethoxy)benzamideHCID 18522661Acetone cardice

Product 1

HCID 103090253,4-Difluoro-2-[2-fluoro-4-(hydroxymethyl)anilino]-N-(2-hydroxyethoxy)benzamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

The product of Example 4, 3,4-Difluoro-2-(2-fluoro-4-vinylanilino)-N-(2-hydroxyethoxy)benzamide (170 mg, 0.48 mmol) was dissolved in MeOH (50 mL) and the solution cooled to −78° C. (acetone/dry ice). Ozone was bubbled through the solution until a pale blue-grey solution was obtained, then nitrogen bubbled through the solution until the blue colour disappeared. A solution of NaBH4 (92 mg, 2.41 mmol) in MeOH (10 mL) was added, the reaction mixture removed from the cold bath and allowed to stir for 0.5 h. at RT. The MeOH was removed from the mixture under reduced pressure and the resulting residue partitioned between EtOAc (50 mL) and 1 M HCl (50 mL). The EtOAc layer was washed with water (50 mL) and brine (50 mL), then dried (Na2SO4) and the solvent removed under reduced pressure to afford an oil which was purified by chromatography on silica gel (10% EtOAc as eluant). 3,4-Difluoro-2-[2-fluoro-4-(hydroxymethyl)anilino]-N-(2-hydroxyethoxy)benzamide was isolated as a pale yellow crystalline solid (99 mg, 58%); m.p. (Et2O/hexane) 108-1 10C. 1H NMR [400 MHz, (CD3)2SO] δ 11.86 (br s, 1 H), 8.74 (br s, 1 H), 7.44-7.37 (m, 1 H), 7.16-7.08 (m, 2 H), 7.02-6.97 (m, 1 H), 6.86 (ddd, J=8.6, 8.6, 4.5 Hz, 1 H), 5.18 (t, J=5.7 Hz, 1 H), 4.71 (br s, 1 H), 4.43 (d, J=5.8 Hz, 2 H), 3.85 (t, J=4.7 Hz, 2 H), 3.60-3.52 (m, 2 H). Anal. calcd. for C16H15F3N2O4: C, 53.9; H, 4.2; N, 7.9. Found C, 54.2; H, 4.6; N, 7.6.

Workup

  1. customOzone was bubbled through the solution until a pale blue-grey solution
  2. customwas obtained
  3. customnitrogen bubbled through the solution until the blue colour
  4. customthe reaction mixture removed from the cold bath
  5. customThe MeOH was removed from the mixture under reduced pressure
  6. customthe resulting residue partitioned between EtOAc (50 mL) and 1 M HCl (50 mL)
  7. washThe EtOAc layer was washed with water (50 mL) and brine (50 mL)
  8. dry with materialdried (Na2SO4)
  9. customthe solvent removed under reduced pressure
  10. customto afford an oil which
  11. customwas purified by chromatography on silica gel (10% EtOAc as eluant)

Sources & evidence

ORD record
ord-06b7c47f867e4d2990cd13563280ed1e
Source dataset
uspto-grants-2005_05
Patent number
US06891066B2

Reaction notes

Loading…