Acetic Acid → HCID 67051627, compound

HRID 1672969Notes

Reaction equation

HRID 1672969 reaction equation
C([C:3]1([C:17]2([OH:28])[CH2:20][N:19]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:18]2)[CH2:8][CH2:7][CH2:6][CH:5]([CH3:9])[N:4]1[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)#N.C(O)(=O)C.C([BH3-])#N.[Na+]>C(O)C>[OH:28][C:17]1([CH:3]2[CH2:8][CH2:7][CH2:6][CH:5]([CH3:9])[N:4]2[CH2:10][C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH2:20][N:19]([C:21]([O:23][C:24]([CH3:25])([CH3:26])[CH3:27])=[O:22])[CH2:18]1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 67051702HCID 67051702, compound

Product 1

HCID 67051627HCID 67051627, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
70 °C

Procedure

To a stirred solution of 1,1-dimethylethyl 3-[2-cyano-6-methyl-1-(phenylmethyl)piperidin-2-yl]-3-hydroxyazetidine-1-carboxylate (180 mg, 0.47 mmol) in ethanol (1 mL) was added acetic acid (53.5 μL, 0.94 mmol) followed by sodium cyanoborohydride (58.7 mg, 0.94 mmol) and the reaction mixture stirred at 70° C. overnight. After cooling to room temperature the suspension was filtered through celite and the solid washed with additional ethanol. The filtrate was concentrated in vacuo and taken up in ethyl acetate (30 mL). The organic layer was washed with 2 M sodium hydroxide solution. The sodium hydroxide layer was separated and washed with ethyl acetate (10 mL). The combined organic layers were washed with brine, dried over anhydrous magnesium sulfate and concentrated in vacuo to give crude 1,1-dimethylethyl 3-hydroxy-3-[6-methyl-1-(phenylmethyl)piperidin-2-yl]azetidine-1-carboxylate as yellow oil (60 mg, 36% yield). Crude product was used further without purification. 1H NMR (400 MHz, CDCl3): 7.22-7.35 (m, 5H), 4.08 (d, 1H), 3.85-3.96 (m, 3H), 3.57 (d, 1H), 3.33-3.36 (m, 1H), 2.91-3.06 (m, 2H), 1.63-1.70 (m, 4H), 1.44 (s, 9H), 1.23 (d, 3H), 1.05 (d, 2H); MS (EI) for C21H32N2O3: 361 (MH+).

Workup

  1. temperatureAfter cooling to room temperature the suspension
  2. filtrationwas filtered through celite
  3. washthe solid washed with additional ethanol
  4. concentrationThe filtrate was concentrated in vacuo
  5. washThe organic layer was washed with 2 M sodium hydroxide solution
  6. customThe sodium hydroxide layer was separated
  7. washwashed with ethyl acetate (10 mL)
  8. washThe combined organic layers were washed with brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a75128b9dec64846b8ca93bcd86a004e
Source dataset
uspto-grants-2011_08
Patent number
US07999006B2

Reaction notes

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