Methyl iodide → tert-butyl-(3R,4R)-4-(4-fluorophenyl)-3-methoxy-piperidine-1-carboxylate

HRID 1518968Notes

Reaction equation

HRID 1518968 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[C@@H:10]([OH:21])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:24]I>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([C:14]2[CH:15]=[CH:16][C:17]([F:20])=[CH:18][CH:19]=2)[C@@H:10]([O:21][CH3:24])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 897142794-(4-Fluoro-phenyl)-3-hydroxy-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 117737848tert-butyl-(3R,4R)-4-(4-fluorophenyl)-3-methoxy-piperidine-1-carboxylateYield 112.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Dissolve tert-butyl-(3R,4R)-4-(4-fluorophenyl)-3-hydroxy-piperidine-1-carboxylate (496 mg, 1.51 mmol) in THF (3 mL) and cool to 0° C. in an ice water bath. Add sodium hydride (84.6 mg, 2.12 mmol), stir for 30 min, and then add methyl iodide (141 uL, 2.27 mmol). Warm to ambient temperature and stir for 5 hours. Quench the reaction with water (5 mL) and separate layers. Extract aqueous layer three times with methyl tert-butyl ether (8 mL), combine organic extracts; dry over magnesium sulphate; filter; collect the filtrate; and concentrate under vacuum to give the title product as a yellow oil (525 mg, 99.9%). MS (m/z): 210 (M+1-Boc).

Workup

  1. temperatureWarm to ambient temperature
  2. customQuench
  3. customthe reaction with water (5 mL)
  4. customseparate layers
  5. dry with materialdry over magnesium sulphate
  6. filtrationfilter
  7. customcollect the filtrate
  8. concentrationand concentrate under vacuum

Sources & evidence

ORD record
ord-75b98748107e42758dc7bea6aee37500
Source dataset
uspto-grants-2015_07
Patent number
US09073856B2

Reaction notes

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