Acetonitrile → HCID 90406318, compound

HRID 2277076Notes

Reaction equation

HRID 2277076 reaction equation
[CH3:1][C:2]#[N:3].C([O-])(C)(C)C.[K+].C[O:11][C:12]([C:14]1[CH:15]=[C:16]([CH:32]=[CH:33][CH:34]=1)[O:17][CH2:18][CH:19]1[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]1)=O>C1COCC1>[C:2]([CH2:1][C:12]([C:14]1[CH:15]=[C:16]([CH:32]=[CH:33][CH:34]=1)[O:17][CH2:18][CH:19]1[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:29])([CH3:30])[CH3:31])=[O:26])[CH2:21][CH2:20]1)=[O:11])#[N:3]

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 23665647Potassium tert-butoxideHCID 67543885HCID 67543885, compound

Product 1

HCID 90406318HCID 90406318, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

CH3CN (0.25 mL, 4.79 mmol) was added to a cold (−78° C.) solution of t-BuO−K+ in THF (1M, 5.0 mL, 5.0 mmol) under Ar and the reaction mixture was stirred for 5 mins. Solution of tert-butyl 4-((3-(methoxycarbonyl)phenoxy)methyl)piperidine-1-carboxylate (1.01 g, 2.86 mmol) in anhydrous THF (7 mL) was added to the reaction mixture and the resulting mixture was stirred at −78° C. for 10 min, then warmed to room temperature over 30 mins. The reaction mixture was quenched with 5% aqueous NaHSO4 and extracted twice with tert-butyl methyl ether. Combined organic layers were washed with brine and concentrated under reduced pressure. Purification by flash chromatography (20%-80% EtOAc-hexanes gradient) gave tert-butyl 4-((3-(2-cyanoacetyl)phenoxy)methyl)piperidine-1-carboxylate as a white solid. Yield (0.55 g, 54%); 1H NMR (400 MHz, DMSO-d6) δ 7.39-7.51 (m, 3H), 7.23-7.28 (m, 1H), 4.73 (s, 2H), 3.84-4.00 (m, 2H), 3.90 (d, J=6.26 Hz, 2H), 2.60-2.80 (m, 2H), 1.86-1.97 (m, 1H), 1.70-1.78 (m, 2H), 1.38 (s, 9H), 1.08-1.23 (m, 2H).

Workup

  1. stirringthe resulting mixture was stirred at −78° C. for 10 min
  2. customThe reaction mixture was quenched with 5% aqueous NaHSO4
  3. extractionextracted twice with tert-butyl methyl ether
  4. washCombined organic layers were washed with brine
  5. concentrationconcentrated under reduced pressure
  6. customPurification by flash chromatography (20%-80% EtOAc-hexanes gradient)

Sources & evidence

ORD record
ord-858354113d2e4ba38832ab0bf0838ac7
Source dataset
uspto-grants-2015_09
Patent number
US09133154B2

Reaction notes

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