Reaction #58790

Reaction equation

gabapentin hydrochloride

Thionyl chloride

gabapentin hydrochloride

thionyl chloride

gabapentin

benzyl alcohol

gabapentin hydrochloride

thionyl chloride

gabapentin hydrochloride

→

product ( 6 )

Yield 91.0%

Benzyl 1-Aminomethyl-1-Cyclohexane Acetate Hydrochloride

Yield 91.0%

Solvents

ethyl ether

Conditions

Workup

1. 1
   OtherA dry 500 mL, three-necked, round-bottomed flask was fitted with a magnetic stirring bar and a 60 mL pressure-equalizing addition funnel
2. 2
   Otherflushed with nitrogen gas
3. 3
   workup.STIRRINGto stir at room temperature for 4 h (LC/MS
4. 4
   Temperaturecooled to 0° C.
5. 5
   workup.STIRRINGwhile stirring
6. 6
   OtherWhite crystalline solid formed
7. 7
   Filtrationwhich was collected by filtration
8. 8
   OtherThe crude compound was recrystallized from a mixture of ethanol and ethyl ether (50 mL: 150 mL.) Finally the white crystals
9. 9
   Washwere washed with 250 mL of ethyl acetate

Procedure

A dry 500 mL, three-necked, round-bottomed flask was fitted with a magnetic stirring bar and a 60 mL pressure-equalizing addition funnel and flushed with nitrogen gas. The flask was charged with gabapentin (17.1 g, 0.1 mol) and benzyl alcohol (128 mL, 1.18 mol) and the mixture was cooled to 0° C. with an ice-water bath. Thionyl chloride (51.8 mL, 77.25 g, 0.65 mol) was added dropwise to the stirred solution over a period of 1 h. The reaction was monitored by LC/MS, with product and unreacted gabapentin hydrochloride being observed. After stirring at room temperature for 3.5 days the reaction mixture contained residual gabapentin hydrochloride (by LC/MS). Additional thionyl chloride (20 mL, 30 g, 0.25 mol) was added at 0° C., and the reaction mixture allowed to stir at room temperature for another 12 h (LC/MS shows traces of residual gabapentin hydrochloride). A final portion of thionyl chloride (10 mL, 15 g, 0.12 mol) was added at 0° C. and the reaction mixture allowed to stir at room temperature for 4 h (LC/MS showed no remaining gabapentin hydrochloride). The reaction mixture was then diluted with ethyl ether (200 mL) and cooled to 0° C. while stirring. White crystalline solid formed, which was collected by filtration. The crude compound was recrystallized from a mixture of ethanol and ethyl ether (50 mL: 150 mL.) Finally the white crystals were washed with 250 mL of ethyl acetate to give product (6) as a white solid (27 g, 91% yield). 1H NMR (CDCl3, 400 MHz.): δ 1.43-1.52 (m, 10H), 2.64 (s, 2H), 3.08 (d, 2H), 6.04 (br. s, 1H), 7.25-7.33 (m, 5H), 8.44 (br. s, 3H). MS (ESI) m/z 262.26 (M+H+).

Source