Water → (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-hydroxyacetoxy)ethyl)pyridine 1-oxide

HRID 1776555Notes

Reaction equation

HRID 1776555 reaction equation
[Cl:1][C:2]1[CH:3]=[N+:4]([O-:50])[CH:5]=[C:6]([Cl:49])[C:7]=1[CH2:8][C@@H:9]([C:34]1[CH:39]=[CH:38][C:37]([O:40][CH:41]([F:43])[F:42])=[C:36]([O:44][CH2:45][CH:46]2[CH2:48][CH2:47]2)[CH:35]=1)[O:10][C:11](=[O:33])[CH2:12][O:13]C(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>C(Cl)Cl.Br>[Cl:49][C:6]1[CH:5]=[N+:4]([O-:50])[CH:3]=[C:2]([Cl:1])[C:7]=1[CH2:8][C@@H:9]([C:34]1[CH:39]=[CH:38][C:37]([O:40][CH:41]([F:43])[F:42])=[C:36]([O:44][CH2:45][CH:46]2[CH2:48][CH2:47]2)[CH:35]=1)[O:10][C:11](=[O:33])[CH2:12][OH:13]

Participants

5

Reactant 2

HCID 962WaterHCID 86679511(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(trityloxy)acetoxy)ethyl)pyridine 1-oxide

Product 1

HCID 86679512(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-hydroxyacetoxy)ethyl)pyridine 1-oxideYield 76%

Reagents, catalysts & solvents 2

HCID 260Hydrogen BromideCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(trityloxy)acetoxy)ethyl)pyridine 1-oxide (4.0 g, 5.55 mmol) in DCM (1 Lt) cooled at 0° C., 160 drops of 48% HBr were added, and the reaction was stirred for 1 hour (temperature below 10° C.). Water was added to the mixture, the organic phase was separated, dried over Na2SO4 and evaporated under vacuum (bath temperature=25° C.). The crude compound was dissolved in DCM, and hexanes was added. The white precipitate thus formed was filtered and washed with plenty of hexanes. After drying, (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-hydroxyacetoxy)ethyl)pyridine 1-oxide was obtained (2.26 g, 4.73 mmol, 76% yield, MS/ESI+ 478.0 [MH]+) and used in the following step without further purification.

Workup

  1. customthe organic phase was separated
  2. dry with materialdried over Na2SO4
  3. customevaporated under vacuum (bath temperature=25° C.)
  4. dissolutionThe crude compound was dissolved in DCM
  5. additionhexanes was added
  6. customThe white precipitate thus formed
  7. filtrationwas filtered
  8. washwashed with plenty of hexanes
  9. customAfter drying

Sources & evidence

ORD record
ord-491b4fc5663d43ed82d4d519a36de860
Source dataset
uspto-grants-2016_02
Patent number
US09265768B2

Reaction notes

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