Sodium Bicarbonate → (S)-benzyl 3-(tert-butoxycarbonylamino)-5-ethylidenepiperidine-1-carboxylate

HRID 1920171Notes

Reaction equation

HRID 1920171 reaction equation
[CH3:1][C:2](C)([O-])C.[K+].[C:7]([O:11][C:12]([NH:14][C@H:15]1[CH2:20][C:19](=O)[CH2:18][N:17]([C:22]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[O:23])[CH2:16]1)=[O:13])([CH3:10])([CH3:9])[CH3:8].C(=O)(O)[O-].[Na+]>[Br-].C([P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)C.C1COCC1>[C:7]([O:11][C:12]([NH:14][C@H:15]1[CH2:20][C:19](=[CH:1][CH3:2])[CH2:18][N:17]([C:22]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[O:23])[CH2:16]1)=[O:13])([CH3:10])([CH3:9])[CH3:8]

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 23665647Potassium tert-butoxideHCID 68922849(S)-benzyl 3-(tert-butoxycarbonylamino)-5-oxopiperidine-1-carboxylate

Product 1

HCID 68922866(S)-benzyl 3-(tert-butoxycarbonylamino)-5-ethylidenepiperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 73727Phosphonium, ethyltriphenyl-, bromide (1:1)CatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a suspension of ethyltriphenylphosphonium bromide (11 eq) in 14 mL of THF was added potassium tert-butoxide (10 eq) at room temperature. The reaction mixture was stirred at that temperature for 20 minutes. Then the reaction was cooled to 0° C., and (S)-benzyl 3-(tert-butoxycarbonylamino)-5-oxopiperidine-1-carboxylate (1 eq) in 7 mL of THF was added to the reaction mixture. The reaction was allowed to warm up room temperature. After being stirred for 40 minutes, the reaction mixture was poured into aq. sodium bicarbonate and extracted with ethyl acetate. The organic layer was separated and washed with brine, then dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The crude residue was purified by flash chromatography (EtOAc:hexanes=2:1) to yield (S)-benzyl 3-(tert-butoxycarbonylamino)-5-ethylidenepiperidine-1-carboxylate. LC/MS (m/z): 261.2 (MH+-100), Rt: 1.12 min. HPLC: Rt: 4.31 min.

Workup

  1. temperatureto warm up room temperature
  2. stirringAfter being stirred for 40 minutes
  3. extractionextracted with ethyl acetate
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried over anhydrous MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude residue was purified by flash chromatography (EtOAc:hexanes=2:1)

Sources & evidence

ORD record
ord-69f2975ecbb946dbb636eee8af1b2de9
Source dataset
uspto-grants-2012_05
Patent number
US08168794B2

Reaction notes

Loading…