Trifluoroacetic acid → (S)-3,5-dichloro-4-(2-(4-(difluoromethoxy)-3-hydroxyphenyl)-2-(thiophene-2-carbonyloxy)ethyl)pyridine 1-oxide

HRID 59763Notes

Reaction equation

HRID 59763 reaction equation
[Cl:1][C:2]1[CH:3]=[N+:4]([O-:34])[CH:5]=[C:6]([Cl:33])[C:7]=1[CH2:8][C@@H:9]([C:18]1[CH:23]=[CH:22][C:21]([O:24][CH:25]([F:27])[F:26])=[C:20]([O:28]CC2CC2)[CH:19]=1)[O:10][C:11]([C:13]1[S:14][CH:15]=[CH:16][CH:17]=1)=[O:12].FC(F)(F)C(O)=O>C(Cl)Cl>[Cl:33][C:6]1[CH:5]=[N+:4]([O-:34])[CH:3]=[C:2]([Cl:1])[C:7]=1[CH2:8][C@@H:9]([C:18]1[CH:23]=[CH:22][C:21]([O:24][CH:25]([F:27])[F:26])=[C:20]([OH:28])[CH:19]=1)[O:10][C:11]([C:13]1[S:14][CH:15]=[CH:16][CH:17]=1)=[O:12]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 72706559(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(thiophene-2-carbonyloxy)ethyl)pyridine 1-oxide2×

Product 1

HCID 86703869(S)-3,5-dichloro-4-(2-(4-(difluoromethoxy)-3-hydroxyphenyl)-2-(thiophene-2-carbonyloxy)ethyl)pyridine 1-oxideYield 41.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(thiophene-2-carbonyloxy)ethyl)pyridine 1-oxide (180 mg, 0.339 mmol) (Compound 21), prepared as previously described in Example 5, Scheme 5, Table 3, was treated with trifluoroacetic acid (TFA) (4 mL, 51.9 mmol), and the resulting solution was stirred at room temperature for 2.5 hours. The reaction mixture was diluted with CH2Cl2 (40 mL) and washed with water (3×40 mL). The organic layer was died over Na2SO4 and evaporated to dryness. The residue was purified by chromatography on SiO2 (CH2Cl2:AcOEt=3:2) to afford (S)-3,5-dichloro-4-(2-(4-(difluoromethoxy)-3-hydroxyphenyl)-2-(thiophene-2-carbonyloxy)ethyl)pyridine 1-oxide (83) (67 mg, 0.141 mmol, 41.4% yield, MS/ESI+474.99 [MH]+)

Workup

  1. washwashed with water (3×40 mL)
  2. customevaporated to dryness
  3. customThe residue was purified by chromatography on SiO2 (CH2Cl2:AcOEt=3:2)

Sources & evidence

ORD record
ord-1456d2fe946c43e7bfd9364c105e5c9c
Source dataset
uspto-grants-2016_09
Patent number
US09440954B2

Reaction notes

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