Benzylamine → (7S,8aR)-2-benzyl-7-hydroxyhexahydropyrrolo[1,2-a]pyrazine-1,4-dione

HRID 1184569Notes

Reaction equation

HRID 1184569 reaction equation
Cl[CH2:2][C:3]([N:5]1[CH2:9][C@@H:8]([OH:10])[CH2:7][C@@H:6]1[C:11]([O:13]C)=O)=[O:4].[CH2:15]([NH2:22])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(N(CC)CC)C>C(OCCO)C>[CH2:15]([N:22]1[CH2:2][C:3](=[O:4])[N:5]2[CH2:9][C@@H:8]([OH:10])[CH2:7][C@@H:6]2[C:11]1=[O:13])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 7504BenzylamineHCID 8471TriethylamineHCID 68783748methyl (2R,4S)-1-(2-chloroacetyl)-4-hydroxypyrrolidine-2-carboxylate

Product 1

HCID 89466235(7S,8aR)-2-benzyl-7-hydroxyhexahydropyrrolo[1,2-a]pyrazine-1,4-dione

Reagents, catalysts & solvents 1

HCID 8076Glycol monoethyl etherSolvent

Procedure

To a solution of Example 65B (200 g, 0.90 mol, 1 equivalent) in 2-ethoxyethanol (3.2 L), benzylamine (120 mL, 1.09 mol, 1.2 equivalents) was added. To this mixture, triethylamine (152 mL, 1.08 mol, 1.28 equivalents) was added, and the mixture was refluxed for 20 hours. The reaction mixture was cooled and concentrated under reduced pressure to afford crude product. This crude material was purified by column chromatography on silica gel using a mixture of methanol-ethyl acetate gradient (0-10%) to afford the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 2.11 (m, 1H), 2.46 (m, 1H), 3.50 (m, 2H), 3.73 (d, 1H, J=16), 3.76 (m, 1H), 4.00 (d, 1H, J=16), 4.45 (d, 1H, J=15), 4.50 (m, 2H), 4.72 (d, 1H, J=15), 7.30 (m, 5H).

Workup

  1. temperaturethe mixture was refluxed for 20 hours
  2. temperatureThe reaction mixture was cooled
  3. concentrationconcentrated under reduced pressure
  4. customto afford crude product
  5. customThis crude material was purified by column chromatography on silica gel using
  6. additiona mixture of methanol-ethyl acetate gradient (0-10%)

Sources & evidence

ORD record
ord-1c757de01d8c4bd3b356fbc137d69e95
Source dataset
uspto-grants-2014_03
Patent number
US08669255B2

Reaction notes

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