Methyl morpholine oxide → 3-bromo-4-[(2,4-difluorobenzyl)oxy]-1-(2,6-difluorophenyl)-5-(1,2-dihydroxyethyl)-6-methylpyridin-2(1H)-one

HRID 1867106Notes

Reaction equation

HRID 1867106 reaction equation
[Br:1][C:2]1[C:3](=[O:29])[N:4]([C:21]2[C:26]([F:27])=[CH:25][CH:24]=[CH:23][C:22]=2[F:28])[C:5]([CH3:20])=[C:6]([CH:18]=[CH2:19])[C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17].C[N+]1([O-])CCOCC1.C(#N)C.[OH2:41].[OH2:42].CC(C)=O>[Os](=O)(=O)(=O)=O>[Br:1][C:2]1[C:3](=[O:29])[N:4]([C:21]2[C:22]([F:28])=[CH:23][CH:24]=[CH:25][C:26]=2[F:27])[C:5]([CH3:20])=[C:6]([CH:18]([OH:42])[CH2:19][OH:41])[C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17]

Participants

6

Reactant 4

HCID 82029Methyl morpholine oxideHCID 18366337Propan-2-one--water (1/1)HCID 18373917Acetonitrile--water (1/1)HCID 220501993-bromo-4-[(2,4-difluorobenzyl)oxy]-1-(2,6-difluorophenyl)-6-methyl-5-vinylpyridin-2(1H)-one

Product 1

HCID 220500393-bromo-4-[(2,4-difluorobenzyl)oxy]-1-(2,6-difluorophenyl)-5-(1,2-dihydroxyethyl)-6-methylpyridin-2(1H)-one

Reagents, catalysts & solvents 1

HCID 30318Osmium TetroxideCatalyst

Procedure

To a room temperature solution of 3-bromo-4-[(2,4-difluorobenzyl)oxy]-1-(2,6-difluorophenyl)-6-methyl-5-vinylpyridin-2(1H)-one (0.970 g, 2.07 mmol) in water/acetone 1:3 (8.7 mL) was added, sequentially, osmium tetroxide (0.110 g, 0.433 mmol) and N-methyl morpholine oxide (1.32 g, 11.2 mmol). The resulting solution was stirred for one hour until complete consumption of starting material by LCMS analysis, and the reaction was concentrated in vacuo. The resulting dark residue was subjected to SiO2 chromatography with ethyl acetate/hexanes (3:7) to furnish a solid. 1H NMR (400 MHz, CDCl3) δ 7.59 (app q, J=8.2 Hz, 1H), 7.45 (ddd, J=14.7, 8.5, 6.8 Hz, 1H), 7.08 (app t, J=8.5 Hz, 2H), 6.94 (app t, J=8.2 Hz, 1H), 6.88 (app t, J=8.5 Hz, 1H), 5.31 (AB-q, J=10.6 Hz, Δ=38.3 Hz, 2H), 5.07 (dd, J=9.1, 3.8 Hz, 1H), 3.83 (t, J=10.8 Hz, 1H), 3.60 (dd, J=11.4, 3.9 Hz, 1H), 2.94 (br s, 1H), 2.16 (s, 3H); LC/MS C-18 column, tr=2.26 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50° C.). ES-MS m/z 502 (M+H). ES-HRMS m/z 502.0276 (M+H calcd for C21H17BrF4NO4 requires 502.0272).

Workup

  1. concentrationthe reaction was concentrated in vacuo
  2. customto furnish a solid

Sources & evidence

ORD record
ord-f57159ee611f413d9cb66dad8e30a9d1
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

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