Ethyl 4-oxo-1-piperidinecarboxylate → HCID 24883127, compound

HRID 2421077Notes

Reaction equation

HRID 2421077 reaction equation
[CH: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])([CH3:3])[CH3:2].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-]>[CH: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])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 34767Ethyl 4-oxo-1-piperidinecarboxylateHCID 5003444Sodium cyanoborohydride2×HCID 59025433HCID 59025433, compound

Product 1

HCID 24883127HCID 24883127, compoundYield 23.8%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 887MethanolSolvent2×

Procedure

(3aS,7aS)-1-isopropyl-3-piperidin-4-yloctahydro-2H-benzimidazol-2-one (85 mg, 0.3 mmol) was dissolved in MeOH (2 mL) and ethyl 4-oxopiperidine-1-carboxylate (48 μL, 0.32 mmol) was added. A solution of sodium cyanoborohydride (31 mg, 0.45 mmol) and zinc chloride (20 mg, 0.15 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) and was washed with 1N NaOH (5 mL), brine and then dried and concentrated in vacuo. The residue was purified by high pH prep LCMS to provide the title compound (30 mg). Free Base-1H NMR (400 MHz, METHANOL-D4): δ ppm 1.14 (dd, J=6.84, 5.27 Hz, 6H), 1.20 (t, J=7.23 Hz, 3H), 1.28-1.45 (m, 6H), 1.54 (d, J=12.50 Hz, 1H), 1.61-1.69 (m, 1H), 1.75-1.92 (m, 6H), 2.12-2.32 (m, 4H), 2.38-2.52 (m, 1H), 2.64-2.81 (m, 2H), 2.80-2.92 (m, 2H), 2.92-3.05 (m, 2H), 3.52-3.65 (m, 1H), 3.83-3.98 (m, 1H), 4.05 (q, J=7.03 Hz, 2H), 4.13 (d, J=13.28 Hz, 2H). MS (M+1): 421.4

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. washwas washed with 1N NaOH (5 mL), brine
  5. customdried
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by high pH

Sources & evidence

ORD record
ord-57114f8333464d34a42ac872247f4878
Source dataset
uspto-grants-2011_06
Patent number
US07956069B2

Reaction notes

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