Dimethyl Sulfide → 3-[2,4-Bis(trifluoromethyl)benzyl]-3-azabicyclo[3.3.1]nonane-7-carbaldehyde

HRID 1620511Notes

Reaction equation

HRID 1620511 reaction equation
C(Cl)(=O)C(Cl)=O.CSC.[F:10][C:11]([F:35])([F:34])[C:12]1[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][C:13]=1[CH2:14][N:15]1[CH2:22][CH:21]2[CH2:23][CH:17]([CH2:18][CH:19]([CH2:24][OH:25])[CH2:20]2)[CH2:16]1.[OH-].[Na+]>C1COCC1.C(N(CC)CC)C>[F:35][C:11]([F:10])([F:34])[C:12]1[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][C:13]=1[CH2:14][N:15]1[CH2:16][CH:17]2[CH2:23][CH:21]([CH2:20][CH:19]([CH:24]=[O:25])[CH2:18]2)[CH2:22]1

Participants

7

Reactant 4

HCID 1068Dimethyl SulfideHCID 14798Sodium HydroxideHCID 65578Oxalyl chlorideHCID 86678703{3-[2,4-Bis(trifluoromethyl)benzyl]-3-azabicyclo[3.3.1]non-7-yl}methanol

Product 1

HCID 866787043-[2,4-Bis(trifluoromethyl)benzyl]-3-azabicyclo[3.3.1]nonane-7-carbaldehydeYield 5.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of oxalyl chloride (1.19 mL) in THF (34.7 mL) was cooled to −78° C., and dimethyl sulfide (1.48 mL) was added dropwise. The reaction mixture was stirred at −78° C. for 20 min, and a solution of {3-[2,4-bis(trifluoromethyl)benzyl]-3-azabicyclo[3.3.1]non-7-yl}methanol (2.65 g) in THF (20 mL) was added dropwise. The mixture was warmed to 0° C., stirred for 30 min, cooled again to −78° C., and triethylamine (4.84 mL) was added. The reaction mixture was stirred at room temperature for 1 hr, poured into 1M aqueous sodium hydroxide solution, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (0.135 g).

Workup

  1. temperatureThe mixture was warmed to 0° C.
  2. stirringstirred for 30 min
  3. temperaturecooled again to −78° C.
  4. stirringThe reaction mixture was stirred at room temperature for 1 hr
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe extract was washed with saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customthe solvent was evaporated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-f83c986f83a949f69ea3b39b58670ce0
Source dataset
uspto-grants-2014_07
Patent number
US08772277B2

Reaction notes

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