HCID 86679476, compound → (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)-phenyl)-2-(3-hydroxy propanoyloxy)ethyl)pyridine 1-oxide

HRID 1776521Notes

Reaction equation

HRID 1776521 reaction equation
[Cl:1][C:2]1[CH:3]=[N+:4]([O-:51])[CH:5]=[C:6]([Cl:50])[C:7]=1[CH2:8][C@@H:9]([C:35]1[CH:40]=[CH:39][C:38]([O:41][CH:42]([F:44])[F:43])=[C:37]([O:45][CH2:46][CH:47]2[CH2:49][CH2:48]2)[CH:36]=1)[O:10][C:11](=[O:34])[CH2:12][CH2:13][O:14]C(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>C(Cl)Cl.Br>[Cl:50][C:6]1[CH:5]=[N+:4]([O-:51])[CH:3]=[C:2]([Cl:1])[C:7]=1[CH2:8][C@@H:9]([C:35]1[CH:40]=[CH:39][C:38]([O:41][CH:42]([F:44])[F:43])=[C:37]([O:45][CH2:46][CH:47]2[CH2:49][CH2:48]2)[CH:36]=1)[O:10][C:11](=[O:34])[CH2:12][CH2:13][OH:14]

Participants

4

Reactant 1

HCID 86679476HCID 86679476, compound

Product 1

HCID 86679477(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)-phenyl)-2-(3-hydroxy propanoyloxy)ethyl)pyridine 1-oxideYield 77.4%

Reagents, catalysts & solvents 2

HCID 260Hydrogen BromideCatalystHCID 6344DichloromethaneSolvent

Procedure

To a mixture of (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(trityloxy)propanoyloxy)ethyl)pyridine 1-oxide (0.600 g, 0.817 mmol) and Amberlyst 15 (4.7 meq/g, 0.050 g) in dry DCM (20 ml), 3 drops of HBr 48% were added at RT. After 1 hour, the reaction mixture was washed with NaHCO3 sat. sol. and with brine. The organic layer was dried over Na2SO4, the solvent was removed under reduced pressure and the residue was purified by flash chromatography on silica gel column (DCM:MeOH:32% aq. NH4OH=90:10:1) affording (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)-phenyl)-2-(3-hydroxy propanoyloxy)ethyl)pyridine 1-oxide (0.311 g, 0.632 mmol, 77% yield, MS/ESI+ 492.1 [MH]+).

Workup

  1. washthe reaction mixture was washed with NaHCO3 sat. sol. and with brine
  2. dry with materialThe organic layer was dried over Na2SO4
  3. customthe solvent was removed under reduced pressure
  4. customthe residue was purified by flash chromatography on silica gel column (DCM:MeOH:32% aq. NH4OH=90:10:1)

Sources & evidence

ORD record
ord-03757b52e5eb4d39ac1a3677593874fa
Source dataset
uspto-grants-2016_02
Patent number
US09265768B2

Reaction notes

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