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

HRID 1746351Notes

Reaction equation

HRID 1746351 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 stifling. After several minutes white crystals form, which are collected by filtration. The crude product is recrystallized from a ⅓ (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. filtrationAfter several minutes white crystals form, which are collected by filtration
  5. customThe crude product is recrystallized from a ⅓ (v/v) mixture of ethanol and ethyl ether (2 L)

Sources & evidence

ORD record
ord-a2ef3c1f4a154750980d72540363686c
Source dataset
uspto-grants-2015_10
Patent number
US09150503B2

Reaction notes

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