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

HRID 240419Notes

Reaction equation

HRID 240419 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 17B (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-5e44e8ba50704535b24813c876bc070a
Source dataset
uspto-grants-2014_02
Patent number
US08648074B2

Reaction notes

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