Sodium cyanoborohydride → (3aR,7aS)-1-[1'-(2-methylbenzoyl)-1,4'-bipiperidin-4-yl]octahydro-2H-indol-2-one

HRID 2421088Notes

Reaction equation

HRID 2421088 reaction equation
Cl.[NH:2]1[CH2:7][CH2:6][CH:5]([N:8]2[C@@H:16]3[C@H:11]([CH2:12][CH2:13][CH2:14][CH2:15]3)[CH2:10][C:9]2=[O:17])[CH2:4][CH2:3]1.C[O-].[Na+].[CH3:21][C:22]1[CH:36]=[CH:35][CH:34]=[CH:33][C:23]=1[C:24]([N:26]1[CH2:31][CH2:30][C:29](=O)[CH2:28][CH2:27]1)=[O:25].C([BH3-])#N.[Na+]>CO.[Cl-].[Zn+2].[Cl-]>[CH3:21][C:22]1[CH:36]=[CH:35][CH:34]=[CH:33][C:23]=1[C:24]([N:26]1[CH2:27][CH2:28][CH:29]([N:2]2[CH2:3][CH2:4][CH:5]([N:8]3[C@@H:16]4[C@H:11]([CH2:12][CH2:13][CH2:14][CH2:15]4)[CH2:10][C:9]3=[O:17])[CH2:6][CH2:7]2)[CH2:30][CH2:31]1)=[O:25]

Participants

7

Reactant 4

HCID 5003444Sodium cyanoborohydrideHCID 10942334Sodium MethoxideHCID 178963611-(2-methylbenzoyl)piperidin-4-oneHCID 67215388(3aR,7aS)-1-piperidin-4-yloctahydro-2H-indol-2-one hydrochloride

Product 1

HCID 24883242(3aR,7aS)-1-[1'-(2-methylbenzoyl)-1,4'-bipiperidin-4-yl]octahydro-2H-indol-2-oneYield 37%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 887MethanolSolvent2×

Procedure

To a solution of (3aR,7aS)-1-piperidin-4-yloctahydro-2H-indol-2-one hydrochloride (70 mg, 0.27 mmol) in MeOH (4 mL) was added sodium methoxide (62 μl, 0.27 mmol) followed by 1-(2-methylbenzoyl)piperidin-4-one (60 mg, 0.27 mmol) and the mixture stirred at room temperature for 10 minutes. A solution containing sodium cyanoborohydride (28 mg, 0.41 mmol) and zinc chloride (18 mg, 0.13 mmol) in MeOH (1 mL) was then added and the mixture stirred at room temperature overnight. The reaction was quenched with water and solvents were removed under reduced pressure. The mixture was diluted in dichloromethane (30 mL) and 1N NaOH (7 mL) was added. The phases were separated and aqueous phase was extracted with dichloromethane (2×20 mL). The combined organic phases were dried and concentrated in vacuo. The crude compound was purified by high pH prep LCMS (40-60%) to provide the title compound as a white solid (37 mg, 37%). 1H NMR (400 MHz, CHLOROFORM-D): δ ppm 1.12-1.41 (m, 5H), 1.42-1.54 (m, 1H), 1.54-1.70 (m, 4H), 1.70-1.99 (m, 7H), 2.11-2.39 (m, 4H), 2.23 (s, 3H), 2.39-2.55 (m, 1H), 2.72 (t, J=12.50 Hz, 1H), 2.78-3.07 (m, 4H), 3.48 (d, J=12.11 Hz, 1H), 3.83-4.01 (m, 1H), 4.80 (d, J=12.50 Hz, 1H), 7.01-7.28 (m, 4H). MS (M+1): 424.2

Workup

  1. additionwas then added
  2. stirringthe mixture stirred at room temperature overnight
  3. customThe reaction was quenched with water and solvents
  4. customwere removed under reduced pressure
  5. additionThe mixture was diluted in dichloromethane (30 mL)
  6. addition1N NaOH (7 mL) was added
  7. customThe phases were separated
  8. extractionaqueous phase was extracted with dichloromethane (2×20 mL)
  9. customThe combined organic phases were dried
  10. concentrationconcentrated in vacuo
  11. customThe crude compound was purified by high pH prep LCMS (40-60%)

Sources & evidence

ORD record
ord-02ee912a8a5149c0a800db6a1aaa42b3
Source dataset
uspto-grants-2011_06
Patent number
US07956069B2

Reaction notes

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