Hydrochloric Acid → 2-{3-[(2,2-Difluoro-2-phenylethyl)amino]-6-chloro-2-fluorophenyl}acetic Acid

HRID 2184194Notes

Reaction equation

HRID 2184194 reaction equation
Cl([O-])=[O:2].[Na+].[F:5][C:6]([F:26])([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH2:7][NH:8][C:9]1[C:10]([F:19])=[C:11]([CH2:16][CH:17]=[O:18])[C:12]([Cl:15])=[CH:13][CH:14]=1.Cl>O.CS(C)=O>[F:26][C:6]([F:5])([C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)[CH2:7][NH:8][C:9]1[C:10]([F:19])=[C:11]([CH2:16][C:17]([OH:2])=[O:18])[C:12]([Cl:15])=[CH:13][CH:14]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 224753142-{3-[(2,2-Difluoro-2-phenylethyl)amino]-6-chloro-2-fluorophenyl}ethanalHCID 23668197Sodium Chlorite

Product 1

HCID 224753482-{3-[(2,2-Difluoro-2-phenylethyl)amino]-6-chloro-2-fluorophenyl}acetic AcidYield 51.3%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent2×

Procedure

A solution of sodium chlorite (692 mg, 6.11 mmol) in H2O (6.1 mL) was added over a period of 30 minutes to a stirred mixture of 2{-3-[(2,2-difluoro-2-phenylethyl)amino]-6-chloro-2-fluorophenyl}ethanal (1.43 g, 4.37 mmol), as prepared in the preceding step, in DMSO (4.5 mL) and of NaH2PO4 (141 mg, 1.18 mmol) in H2O (1.7 mL). After the addition, the mixture was stirred at ambient temperature overnight, acidified with 10 M HCl to pH 1, and extracted with DCM (3 times). The extracts were combined, washed with H2O and brine, dried over Na2SO4, and concentrated in vacuo. The resulting residue was flash chromatographed on silica gel eluting with MeOH/DCM (0, 2, and 4%) to give the title compound (0.77 g, 51% yield) as a pale brown solid. 1H-NMR (400 MHz, CD3OD) δ 7.53-7.51 (m, 2H), 7.44-7.41 (m, 3H), 6.93 (dd, J=8.9, 1.8 Hz, 1H), 6.62 (t, J=9.1 Hz, 1H), 3.80 (t, J=13.7 Hz, 2H), 3.74 (d, J=2.2 Hz, 2H). Mass spectrum (LCMS, ESI) calc'd for C16H14ClF3NO2 (M+H): 344.1. Found: 344.4.

Workup

  1. additionAfter the addition
  2. extractionextracted with DCM (3 times)
  3. washwashed with H2O and brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customchromatographed on silica gel eluting with MeOH/DCM (0, 2, and 4%)

Sources & evidence

ORD record
ord-bae833267f9d4a0a879bed8a0af6573d
Source dataset
uspto-grants-2005_05
Patent number
US06900231B2

Reaction notes

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