Gabapentin → Boc-Tyr Gabapentin

HRID 1991397Notes

Reaction equation

HRID 1991397 reaction equation
[NH:1]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[C@H:2]([C:11]([OH:13])=[O:12])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1.ONC(=O)CCC(N)=O.[CH2:30]1[CH2:35][CH2:34][C:33]([CH2:40][NH2:41])([CH2:36][C:37]([OH:39])=[O:38])[CH2:32][CH2:31]1.[OH-].[Na+]>C(#N)C>[NH:1]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[C@H:2]([C:11]([OH:13])=[O:12])[CH2:3][C:4]1[CH:5]=[CH:6][C:7]([OH:10])=[CH:8][CH:9]=1.[CH2:30]1[CH2:31][CH2:32][C:33]([CH2:40][NH2:41])([CH2:36][C:37]([OH:39])=[O:38])[CH2:34][CH2:35]1

Participants

6

Reactant 4

HCID 3446GabapentinHCID 14798Sodium HydroxideHCID 117439L-Tyrosine, N-(1,1-dimethylethoxy)carbonyl-HCID 18381240N-hydroxysuccinamide

Product 1

HCID 131727014Boc-Tyr GabapentinYield 106.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of Boc-Tyr-OH (4.2 g, 15 mmol) in acetonitrile (100 mL) was added N-hydroxysuccinamide (1.84 g, 16 mmol) and N,N-dicyclohexylcarbodiimide (3.3 g, 16 mmol). The reaction was stirred at ambient temperature for 2 h. The reaction mixture was filtered directly into an aqueous solution (100 mL) of gabapentin (2.7 g, 16 mmol) and sodium hydroxide (640 mg, 16 mmol), and the resulting mixture stirred at ambient temperature for 16 h. The reaction was concentrated under reduced pressure, the residue was dissolved in ethyl acetate/diethyl ether (1/1, 200 mL) and washed with 0.1M aqueous potassium hydrogensulfate (2×200 mL). The organic phase was separated, dried over Na2SO4, filtered, and concentrated to dryness under reduced pressure to afford Boc-Tyr-Gabapentin as a white solid (7.4 g, 16 mmol).

Workup

  1. stirringthe resulting mixture stirred at ambient temperature for 16 h
  2. concentrationThe reaction was concentrated under reduced pressure
  3. dissolutionthe residue was dissolved in ethyl acetate/diethyl ether (1/1, 200 mL)
  4. washwashed with 0.1M aqueous potassium hydrogensulfate (2×200 mL)
  5. customThe organic phase was separated
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-ddf4e2e8a7564921962e60c963eeead9
Source dataset
uspto-grants-2010_01
Patent number
US07645797B2

Reaction notes

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