Water → HCID 66732043, compound

HRID 1963282Notes

Reaction equation

HRID 1963282 reaction equation
O=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][CH3:11])=[O:9])[CH:4]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=2)[CH2:3]1.[N+:23](CS(C1C=CC(C)=CC=1)(=O)=O)#[C-:24].CC(C)([O-])C.[K+].O>COCCOC>[C:24]([CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][CH3:11])=[O:9])[CH:4]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=2)[CH2:3]1)#[N:23]

Participants

6

Reactant 4

HCID 962WaterHCID 161915Tosylmethyl isocyanideHCID 23665647Potassium tert-butoxideHCID 68502902HCID 68502902, compound

Product 1

HCID 66732043HCID 66732043, compoundYield 87.9%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent2×

Conditions

Temperature
-20 °C

Procedure

To a solution of methyl 4-oxo-2-(4-(trifluoromethyl)benzyl)piperidine-1-carboxylate (8.75 g, 27.75 mmol) (Syngene) in DME (100 mL) under nitrogen was added simultaneously 1-(isocyanomethylsulfonyl)-4-methylbenzene (8.13 g, 41.63 mmol) in 100 mL DME and potassium tert-butoxide (83 mL, 83.26 mmol) (1 M) over 30 min at −20 to −10° C. The solution was stirred at −20° C. for 2 h and then allowed to warm to room temperature overnight. To the orange reaction mixture was added water (200 mL), the solution was stirred for 20 min and then extracted with diethyl ether (3×) and EtOAc (3×). The combined organic phases were washed once with brine and then dried over Na2SO4 and evaporated to yield a brown oil. The oil was purified by flash chromatography on silica gel using a gradient of 20-60% EtOAc in heptane as eluent. Methyl 4-cyano-2-(4-(trifluoromethyl)benzyl)piperidine-1-carboxylate (7.96 g, 87.9%) was isolated as a yellow oil.

Workup

  1. temperatureto warm to room temperature overnight
  2. stirringthe solution was stirred for 20 min
  3. extractionextracted with diethyl ether (3×) and EtOAc (3×)
  4. washThe combined organic phases were washed once with brine
  5. dry with materialdried over Na2SO4
  6. customevaporated
  7. customto yield a brown oil
  8. customThe oil was purified by flash chromatography on silica gel using a gradient of 20-60% EtOAc in heptane as eluent

Sources & evidence

ORD record
ord-ed56eb4bf38c442bab61089c1525218e
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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