Water → 4-methylene-1-(tert-butoxycarbonyl)piperidine-2(S)-carboxylic acid benzyl ester

HRID 536581Notes

Reaction equation

HRID 536581 reaction equation
[CH3:1][Si](C)(C)[N-][Si](C)(C)C.[Na+].[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][C:21](=O)[CH2:20][C@H:19]1[C:25]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26])=[O:17])([CH3:14])([CH3:13])[CH3:12].O>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1(C)C=CC=CC=1>[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][C:21](=[CH2:1])[CH2:20][C@H:19]1[C:25]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26])=[O:17])([CH3:14])([CH3:13])[CH3:12]

Participants

6

Reactant 3

HCID 962WaterHCID 2724254Sodium bis(trimethylsilyl)amideHCID 668482142-Benzyl 1-(tert-butyl) (S)-4-oxopiperidine-1,2-dicarboxylate2×

Product 1

HCID 668487244-methylene-1-(tert-butoxycarbonyl)piperidine-2(S)-carboxylic acid benzyl esterYield 57.4%

Reagents, catalysts & solvents 2

HCID 74505Methyltriphenyliphosphonium bromideCatalystHCID 1140TolueneSolvent2×

Procedure

To a suspension of methyl(triphenyl)phosphonium bromide (248 g, 0.69 mol) in anhydrous toluene (1 L) was added sodium hexamethyldisilazide (258 ml, 0.69 mmol) at 0° C., after addition was completed, the reaction mixture was warmed to room temperature, and stirred at room temperature for 1 hour, then cooled to 0° C. and the solution of (S)-4-oxo-piperidine-1,2-dicarboxylic acid 2-benzyl ester 1-tert-butyl ester (intermediate 14, 210 g, 0.63 mol) in anhydrous toluene (0.5 L) was added. The resulting mixture was warmed to room temperature, and stirred at room temperature for 1 hour, added water (500 ml), extracted with ethyl acetate. The combined organic extracts were dried (Na2SO4), filtered and evaporated to obtain a crude that was purified by silica gel chromatography (petroleum ether/ethyl acetate from 10/1 to 5/1). (S)-4-Methylene-piperidine-1,2-dicarboxylic acid 2-benzyl ester 1-tert-butyl ester was obtained as colourless oil (120 g), yield:57.4%.

Workup

  1. additionafter addition
  2. temperaturecooled to 0° C.
  3. temperatureThe resulting mixture was warmed to room temperature
  4. stirringstirred at room temperature for 1 hour
  5. extractionextracted with ethyl acetate
  6. dry with materialThe combined organic extracts were dried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated
  9. customto obtain a crude that
  10. customwas purified by silica gel chromatography (petroleum ether/ethyl acetate from 10/1 to 5/1)

Sources & evidence

ORD record
ord-508af2e2532d4480a47f13dbf0925974
Source dataset
uspto-grants-2014_10
Patent number
US08859608B2

Reaction notes

Loading…