Morpholine → Gabapentin Enacarbil

HRID 30519

Reaction equation

HRID 30519 reaction equation
[C:1]([O:6][CH:7]([O:9][C:10]([NH:12][CH2:13][C:14]1([CH2:20][C:21]([O:23]CC=C)=[O:22])[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1)=[O:11])[CH3:8])(=[O:5])[CH:2]([CH3:4])[CH3:3].N1CCOCC1>C(#N)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:1]([O:6][CH:7]([O:9][C:10]([NH:12][CH2:13][C:14]1([CH2:20][C:21]([OH:23])=[O:22])[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1)=[O:11])[CH3:8])(=[O:5])[CH:2]([CH3:4])[CH3:3]

Participants

5

Reactant 2

HCID 8083MorpholineHCID 9999163Allyl 1-{[(alpha-Isobutanoyloxyethoxy)carbonyl]aminomethyl}-1-Cyclohexane Acetate

Product 1

HCID 9883933Gabapentin Enacarbil

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of compound (15) (1 g, 2.7 mmol) in acetonitrile (10 mL) under nitrogen was added (10 mg, 0.008 mmol) of tetrakis(triphenylphosphine) palladium (0) followed by morpholine (0.28 mL, 0.28 g, 3.2 mmol). After one hour, the solvent was removed in vacuo. The resulting oil was dissolved in diethyl ether (50 mL) and the organic phase was washed with 2N HCl (20 mL), water (20 mL) and brine (20 mL). The ether layer was dried over anhydrous sodium sulfate and concentrated to give an oil, which was purified by column chromatography on silica gel, eluting with 30% ethyl acetate:hexane. The desired product (11) was isolated as a white crystalline solid (0.75 g, 84% yield), m.p 63-64° C.

Workup

  1. customthe solvent was removed in vacuo
  2. dissolutionThe resulting oil was dissolved in diethyl ether (50 mL)
  3. washthe organic phase was washed with 2N HCl (20 mL), water (20 mL) and brine (20 mL)
  4. dry with materialThe ether layer was dried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. customto give an oil, which
  7. customwas purified by column chromatography on silica gel
  8. washeluting with 30% ethyl acetate

Sources & evidence

ORD record
ord-3f5fa7b35b8f40caab56e0df7f730e98
Source dataset
uspto-grants-2008_09
Patent number
US07423169B2

Linked notes

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