Methanol → HCID 45139441, compound

HRID 2401575Notes

Reaction equation

HRID 2401575 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])([C:14](=O)[NH2:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CO>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([CH2:14][NH2:15])([NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 887MethanolHCID 66873235HCID 66873235, compound

Product 1

HCID 45139441HCID 45139441, compoundYield 6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A 1M solution of borane complex in THF (2.25mL, 2.25 mmol) was added to a cooled solution (0° C.) of 4-tert-butoxycarbonylamino-4-carbamoyl-piperidine-1-carboxylic acid tert-butyl ester (107 mg, 0.3 mmol) in THF (4.3 mL). After stirring for 5 minutes at 0° C. the reaction mixture was allowed to warm to room temperature. The reaction mixture was further warmed to 60° C. and stirred overnight. The reaction mixture was cooled to room temperature and methanol (5.1 mL) was added. After stirring for 30 minutes, the solvents were removed by evaporation. The reaction mixture was partitioned between an aqueous saturated solution of ammonium chloride (10 mL) and dichloromethane (10 mL). After further extraction of the aqueous phase with dichloromethane (20 mL), the combined organic phases were dried (Mg2SO4), filtered and concentrated. Flash column chromatography on silica, eluting with 5% methanol in dichloromethane, gave 4-aminomethyl-4-tert-butoxycarbonylamino-piperidine-1-carboxylic acid tert-butyl ester (5.5 mg, 0.017 mmol, 6%). LC-MS (LCT2) m/z 352 [M+Na+], Rt 7.16 min.

Workup

  1. temperatureto warm to room temperature
  2. temperatureThe reaction mixture was further warmed to 60° C.
  3. stirringstirred overnight
  4. temperatureThe reaction mixture was cooled to room temperature
  5. stirringAfter stirring for 30 minutes
  6. customthe solvents were removed by evaporation
  7. customThe reaction mixture was partitioned between an aqueous saturated solution of ammonium chloride (10 mL) and dichloromethane (10 mL)
  8. extractionAfter further extraction of the aqueous phase with dichloromethane (20 mL)
  9. dry with materialthe combined organic phases were dried (Mg2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. washFlash column chromatography on silica, eluting with 5% methanol in dichloromethane

Sources & evidence

ORD record
ord-51698ad8bd2c4772a1fa01a79ceb7088
Source dataset
uspto-grants-2014_08
Patent number
US08796293B2

Reaction notes

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