Methyl morpholine oxide → (2R,3R,4R)-2-[(1R)-1-(3,5-Bis(trifluoromethyl)phenyl)ethoxy]-3-(4-fluorophenyl)-tetrahydropyran-4-carbaldehyde

HRID 746999Notes

Reaction equation

HRID 746999 reaction equation
C[N+]1([O-])CC[O:5]CC1.[F:9][C:10]([F:40])([F:39])[C:11]1[CH:12]=[C:13]([C@H:21]([O:23][C@@H:24]2[C@@H:29]([C:30]3[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=3)[C@H:28]([CH:37]=C)[CH2:27][CH2:26][O:25]2)[CH3:22])[CH:14]=[C:15]([C:17]([F:20])([F:19])[F:18])[CH:16]=1.I([O-])(=O)(=O)=O.[Na+]>O1CCCC1.O.[Os](=O)(=O)(=O)=O>[F:18][C:17]([F:20])([F:19])[C:15]1[CH:14]=[C:13]([C@H:21]([O:23][C@@H:24]2[C@@H:29]([C:30]3[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=3)[C@H:28]([CH:37]=[O:5])[CH2:27][CH2:26][O:25]2)[CH3:22])[CH:12]=[C:11]([C:10]([F:39])([F:40])[F:9])[CH:16]=1

Participants

7

Reactant 3

HCID 82029Methyl morpholine oxideHCID 23667635Sodium periodateHCID 86606910HCID 86606910, compound

Product 1

HCID 86601740(2R,3R,4R)-2-[(1R)-1-(3,5-Bis(trifluoromethyl)phenyl)ethoxy]-3-(4-fluorophenyl)-tetrahydropyran-4-carbaldehydeYield 80.1%

Reagents, catalysts & solvents 3

HCID 30318Osmium TetroxideCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

N-Methylmorpholine N-oxide (1 g, 8.6 mmol) and osmium tetroxide (2 ml, 2.5% solution in tert-butanol) were added to a solution of (2R,3R,4S)-2-[(1R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy]-3-(4-fluorophenyl)-4-vinyl-tetrahydropyran (see Example 147 in WO 00/56727; 2 g, 4.3 mmol) in tetrahydrofuran (25 ml) and water (10 ml). The mixture was stirred at room temperature for one hour before sodium periodate (9 g, 43 mmol) was added. This mixture was stirred for 45 minutes and then filtered through Celite™. The filtrate was diluted with ethyl acetate (50 ml) and washed with brine. The organic extracts were dried and concentrated. The residue was chromatographed on silica gel eluting with ethyl acetate/iso-hexanes to give the title compound (1.6 g, 80%).

Workup

  1. additionwas added
  2. filtrationfiltered through Celite™
  3. additionThe filtrate was diluted with ethyl acetate (50 ml)
  4. washwashed with brine
  5. customThe organic extracts were dried
  6. concentrationconcentrated
  7. customThe residue was chromatographed on silica gel eluting with ethyl acetate/iso-hexanes

Sources & evidence

ORD record
ord-26be5f3b10254e6993a1404530f82af9
Source dataset
uspto-grants-2008_07
Patent number
US07393858B2

Reaction notes

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