Hydrochloric Acid → HCID 10125889, compound

HRID 1793029Notes

Reaction equation

HRID 1793029 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([C:9]([NH:11][O:12][CH2:13][CH2:14][OH:15])=[O:10])[C:3]=1[NH:16][C:17]1[CH:36]=[CH:35][C:20]([C:21](OC2C(F)=C(F)C(F)=C(F)C=2F)=[O:22])=[CH:19][CH:18]=1.[BH4-].[Na+].Cl>C1COCC1.O>[F:1][C:2]1[C:3]([NH:16][C:17]2[CH:36]=[CH:35][C:20]([CH2:21][OH:22])=[CH:19][CH:18]=2)=[C:4]([CH:5]=[CH:6][C:7]=1[F:8])[C:9]([NH:11][O:12][CH2:13][CH2:14][OH:15])=[O:10]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 22025652HCID 22025652, compound

Product 1

HCID 10125889HCID 10125889, compoundYield 37%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

The product of Example 17, Step C, 2,3,4,5,6-pentafluorophenyl 4-[[2,3-difluoro-6-[[(2-hydroxyethoxy)amino]carbonyl]phenyl]amino]benzoate (150 mg, 0.29 mmol) was dissolved in THF (2 mL), then added dropwise to a solution of NaBH4 (110 mg, 2.90 mmol) in water (2 mL). This mixture was stirred at room temperature for 2 hours, acidified with 1 M HCl, and diluted with water (50 mL). The resulting aqueous mixture was extracted with EtOAc (2×50 mL), then the combined EtOAc fractions washed with water (50 mL), saturated NaCl (50 mL), and dried (Na2SO4). The solvent was removed under reduced pressure and the resulting residue purified by column chromatography on flash silica (50% EtOAc/hexanes as eluant) to afford 3,4-difluoro-N-(2-hydroxyethoxy)-2-[[4-(hydroxymethyl)phenyl]amino]benzamide as a cream solid (36 mg, 37%); m.p. (EtOAc/hexanes) 73–77° C. 1H NMR [400 MHz, (CD3)2SO] δ 11.73 (br s, 1 H), 8.68 (br s, 1 H), 7.41–7.35 (m, 1H), 7.15 (d, J=8.5 Hz, 2 H), 7.14–7.06 (m, 1 H), 6.79 (dd, J=8.5, 2.3 Hz, 2 H), 4.99 (t, J=5.7 Hz, 1 H), 4.72 (br s, 1 H), 4.38 (d, J=5.6, 2 H), 3.80 (t, J=4.9 Hz, 2 H), 3.54 (t, J=4.9 Hz, 2 H). Anal. Calcd for C16H16F2N2O4: C, 56.8; H, 4.8; N, 8.3. Found: C, 56.3; H, 4.7; N, 8.1.

Workup

  1. extractionThe resulting aqueous mixture was extracted with EtOAc (2×50 mL)
  2. washthe combined EtOAc fractions washed with water (50 mL), saturated NaCl (50 mL)
  3. dry with materialdried (Na2SO4)
  4. customThe solvent was removed under reduced pressure
  5. customthe resulting residue purified by column chromatography on flash silica (50% EtOAc/hexanes as eluant)

Sources & evidence

ORD record
ord-84f9ed7f26984a379b554b4c90bb3f70
Source dataset
uspto-grants-2006_07
Patent number
US07078438B2

Reaction notes

Loading…