Acetic Acid → Tert-butyl 4-oxo-3-(3-(tetrahydrofuran-2-yl)propanoyl)piperidine-1-carboxylate

HRID 1930724Notes

Reaction equation

HRID 1930724 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[O:11]=[C:12]1[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]1.N1([C:30](=[O:38])[CH2:31][CH2:32][CH:33]2[CH2:37][CH2:36][CH2:35][O:34]2)C=CN=C1.C(O)(=O)C>C1(C)C=CC=CC=1.O>[O:11]=[C:12]1[CH2:13][CH2:14][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:16][CH:17]1[C:30](=[O:38])[CH2:31][CH2:32][CH:33]1[CH2:37][CH2:36][CH2:35][O:34]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 2733832Lithium HexamethyldisilazideHCID 593337451-(1H-imidazol-1-yl)-3-(tetrahydrofuran-2-yl)propan-1-one

Product 1

HCID 59333690Tert-butyl 4-oxo-3-(3-(tetrahydrofuran-2-yl)propanoyl)piperidine-1-carboxylateYield 38.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent2×

Procedure

Lithium bis(trimethylsilyl)amide (2.231 ml, 11.88 mmol) was added to a stirred solution of tert-butyl 4-oxopiperidine-1-carboxylate (1.127 g, 5.66 mmol) in toluene (3 mL) at 0° C. and the resulting mixture was stirred for 2 minutes. 1-(1H-Imidazol-1-yl)-3-(tetrahydrofuran-2-yl)propan-1-one (1.099 g, 5.66 mmol) in toluene (1 mL) was added and the reaction mixture was stirred for 5 minutes before it was quenched with acetic acid (0.972 ml, 16.97 mmol) in water (4 mL). The organic layer was separated and purified by silica flash chromatography using a gradient of ethyl acetate in heptane (0 to 40%) giving tert-butyl 4-oxo-3-(3-(tetrahydrofuran-2-yl)propanoyl)piperidine-1-carboxylate (0.717 g, 38.9%) as the product.

Workup

  1. stirringthe reaction mixture was stirred for 5 minutes before it
  2. customThe organic layer was separated
  3. custompurified by silica flash chromatography

Sources & evidence

ORD record
ord-566de2f90d7f433e9eeefc5257f1e99b
Source dataset
uspto-grants-2012_05
Patent number
US08188101B2

Reaction notes

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