Methyl morpholine oxide → (2R)-4-(5-Formyl-3-trifluoromethyl-pyridin-2-yl)-2-methyl-piperazine-1-carboxylic acid tert-butyl ester

HRID 912965Notes

Reaction equation

HRID 912965 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19]([C:20]([F:23])([F:22])[F:21])=[CH:18][C:17](C=CC(OC)=O)=[CH:16][N:15]=2)[CH2:10][C@H:9]1[CH3:30])=[O:7])([CH3:4])([CH3:3])[CH3:2].C[N+]1([O-])CC[O:35][CH2:34]C1.OS([O-])=O.[Na+]>CC(C)=O.CCCCCC.O=[Os](=O)(=O)=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19]([C:20]([F:21])([F:23])[F:22])=[CH:18][C:17]([CH:34]=[O:35])=[CH:16][N:15]=2)[CH2:10][C@H:9]1[CH3:30])=[O:7])([CH3:3])([CH3:2])[CH3:4]

Participants

7

Reactant 3

HCID 82029Methyl morpholine oxideHCID 23665763Sodium BisulfiteHCID 67400642(2R)-4-[5-(2-Methoxycarbonyl-vinyl)-3-trifluoromethyl-pyridin-2-yl]-2-methyl-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 11501642(2R)-4-(5-Formyl-3-trifluoromethyl-pyridin-2-yl)-2-methyl-piperazine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 3

HCID 30318Osmium TetroxideCatalystHCID 180AcetoneSolventHCID 8058HexaneSolvent

Procedure

A mixture of (2R)-4-[5-(2-methoxycarbonyl-vinyl)-3-trifluoromethyl-pyridin-2-yl]-2-methyl-piperazine-1-carboxylic acid tert-butyl ester from step (d) above (6.02 g, 14 mmol), OsO4 (4.43 mL, 0.7 mmol, 4% in H2O, Aldrich) and N-methylmorpholine N-oxide (1.96 g, 16.8 mmol, Aldrich) in acetone (16 mL) was stirred at room temperature for 5 h. To the mixture was added saturated aqueous solution of NaHSO3 (910 mL) and the mixture was extracted with EtOAc (2×40 mL). The combined organic extracts were washed with brine (20 mL), dried over Na2SO4 and filtered. The filtrate was evaporated in vacuo and the residue was dissolved in dichloromethane (20 mL). To the solution was added Pb(OAc)4 (7.44 g, 16.8 mmol, Aldrich) in one portion and the mixture was stirred at 0° C. for 30 min. The mixture was diluted with hexane (10 mL), filtered through a Celite® pad and the filter cake was washed with 50% EtOAc/hexane. The filtrate was evaporated in vacuo and the residue was purified by silica gel column chromatography, eluting with 30% EtOAc/hexane to give the title compound as a gum. MS (ESI, pos. ion) m/e: 374 (M+1).

Workup

  1. extractionthe mixture was extracted with EtOAc (2×40 mL)
  2. washThe combined organic extracts were washed with brine (20 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. customThe filtrate was evaporated in vacuo
  6. dissolutionthe residue was dissolved in dichloromethane (20 mL)
  7. stirringthe mixture was stirred at 0° C. for 30 min
  8. filtrationfiltered through a Celite® pad
  9. washthe filter cake was washed with 50% EtOAc/hexane
  10. customThe filtrate was evaporated in vacuo
  11. customthe residue was purified by silica gel column chromatography
  12. washeluting with 30% EtOAc/hexane

Sources & evidence

ORD record
ord-1cfc714932a84de7a7b82d4fa08c5007
Source dataset
uspto-grants-2011_09
Patent number
US08026241B2

Reaction notes

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