Ethyl 4-oxo-1-piperidinecarboxylate → HCID 24883126, compound

HRID 2421075Notes

Reaction equation

HRID 2421075 reaction equation
[CH2:1]([N:4]1[C@H:8]2[CH2:9][CH2:10][CH2:11][CH2:12][C@@H:7]2[N:6]([CH:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)[C:5]1=[O:19])[CH:2]=[CH2:3].O=[C:21]1[CH2:26][CH2:25][N:24]([C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH2:23][CH2:22]1.C([BH3-])#N.[Na+]>CO.[Cl-].[Zn+2].[Cl-]>[CH2:1]([N:4]1[C@H:8]2[CH2:9][CH2:10][CH2:11][CH2:12][C@@H:7]2[N:6]([CH:13]2[CH2:14][CH2:15][N:16]([CH:21]3[CH2:26][CH2:25][N:24]([C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH2:23][CH2:22]3)[CH2:17][CH2:18]2)[C:5]1=[O:19])[CH:2]=[CH2:3]

Participants

6

Reactant 3

HCID 34767Ethyl 4-oxo-1-piperidinecarboxylateHCID 5003444Sodium cyanoborohydride2×HCID 59025450HCID 59025450, compound

Product 1

HCID 24883126HCID 24883126, compoundYield 43.4%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 887MethanolSolvent2×

Procedure

(3aS,7aS)-1-allyl-3-piperidin-4-yloctahydro-2H-benzimidazol-2-one (183 mg, 0.69 mmol) was dissolved in MeOH (2 mL) and ethyl 4-oxopiperidine-1-carboxylate (100 μL, 0.66 mmol) was added. A solution of sodium cyanoborohydride (82 mg, 1.19 mmol) and zinc chloride (47 mg, 0.34 mmol) in MeOH (1 mL) was then added drop wise at room temperature. The mixture was then stirred for 3 hours and then more sodium cyanoborohydride (40 mg) was added and the mixture stirred at room temperature over night. The solvent was then removed under reduced pressure and the residue was diluted in dichloromethane (80 mL). Washed with 1N NaOH (5 mL) and brine, dried and concentrated in vacuo. The residue was purified by high pH prep LCMS to provide the title compound (120 mg). 1H NMR (400 MHz, METHANOL-D4) δ ppm 1.24 (t, J=7.03 Hz, 3H), 1.28-1.48 (m, 6H), 1.53-1.64 (m, 1H), 1.65-1.74 (m, 1H), 1.77-1.99 (m, 6H), 1.99-2.10 (m, 1H), 2.22-2.36 (m, 3H), 2.42-2.58 (m, 1H), 2.69-2.86 (m, 3H), 2.89-3.11 (m, 3H), 3.56-3.71 (m, 1H), 3.72-3.78 (m, 2H), 4.09 (q, J=7.16 Hz, 2H), 4.17 (d, J=13.28 Hz, 2H), 5.03-5.26 (m, 2H), 5.62-5.84 (m, 1H). MS (M+1): 419.2

Workup

  1. stirringthe mixture stirred at room temperature over night
  2. customThe solvent was then removed under reduced pressure
  3. additionthe residue was diluted in dichloromethane (80 mL)
  4. washWashed with 1N NaOH (5 mL) and brine
  5. customdried
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by high pH

Sources & evidence

ORD record
ord-7814bb08a2034a54afe25b5a53864a15
Source dataset
uspto-grants-2011_06
Patent number
US07956069B2

Reaction notes

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