Gabapentin → Prop-2-enyl 2-[1-(aminomethyl)cyclohexyl]acetate;hydrochloride

HRID 913208Notes

Reaction equation

HRID 913208 reaction equation
[CH2:1]1[CH2:6][CH2:5][C:4]([CH2:11][NH2:12])([CH2:7][C:8]([OH:10])=[O:9])[CH2:3][CH2:2]1.[CH2:13](O)[CH:14]=[CH2:15].S(Cl)([Cl:19])=O>C(OCC)C>[ClH:19].[NH2:12][CH2:11][C:4]1([CH2:7][C:8]([O:10][CH2:15][CH:14]=[CH2:13])=[O:9])[CH2:3][CH2:2][CH2:1][CH2:6][CH2:5]1

Participants

5

Reactant 3

HCID 3446GabapentinHCID 7858Allyl AlcoholHCID 24386Thionyl Chloride

Product 1

HCID 66743418Prop-2-enyl 2-[1-(aminomethyl)cyclohexyl]acetate;hydrochlorideYield 88.8%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

A dry 3 L, three-neck, round-bottomed flash fitted with a magnetic stirring bar and a 500 mL pressure-equalizing addition funnel is flushed with nitrogen gas. The flask is charged with gabapentin (171 g, 1.0 mol) and allyl alcohol (1 L, 852 g, 14.6 mol) and the entire mixture is cooled to 0° C. in an ice-water bath. Thionyl chloride (225 mL, 360 g, 3.0 mol) is added dropwise over a period of 1 h to the stirred solution. The reaction mixture is allowed to stir at room temperature for 16 h, then is diluted with ethyl ether (2 L) and cooled to 0° C. while stirring. After several minutes white crystals form formed, which are were collected by filtration. The crude product is recrystallized from a 1/3 (v/v) mixture of ethanol and ethyl ether (2 L) to give the product as a white solid (220 g 88%). m.p.: 138-142° C. 1H NMR (CD3OD, 400 MHz): δ 1.36-1.54 (m, 10H), 2.57 (s, 2H), 3.05 (s, 2H), 4.61 (d, J=6 Hz, 2H), 5.22 (dd, J1=10.4 Hz, J2=1.2 Hz, 1H), 5.33 (dd, J1=17.2 Hz, J2=1.4 Hz, 1H), 5.90-6.00 (m, 1H). MS (ESI) m/z 212.0 (M-Cl)+.

Workup

  1. customA dry 3 L, three-neck, round-bottomed flash fitted with a magnetic stirring bar and a 500 mL pressure-equalizing addition funnel
  2. customis flushed with nitrogen gas
  3. temperaturecooled to 0° C.
  4. stirringwhile stirring
  5. customAfter several minutes white crystals form
  6. customformed
  7. filtrationwhich are were collected by filtration
  8. customThe crude product is recrystallized from a 1/3 (v/v) mixture of ethanol and ethyl ether (2 L)

Sources & evidence

ORD record
ord-84a66b5c8bd44c9e9298d3af4a25c8d6
Source dataset
uspto-grants-2011_09
Patent number
US08026279B2

Reaction notes

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