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

HRID 1184559Notes

Reaction equation

HRID 1184559 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 14914600(2S,4R)-methyl 1-(2-chloroacetyl)-4-hydroxypyrrolidine-2-carboxylate

Product 1

HCID 14914605(7R,8aS)-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 54B (75 g, 0.34 mol, 1 equivalent) in 2-ethoxyethanol (1.2 L), benzylamine (44 mL, 0.41 mol, 1.2 equivalents) was added. Triethylamine (60 mL, 0.43 mol, 1.28 equivalents) was then added, and the resultant mixture was refluxed for 12 hours. The reaction mixture was cooled and concentrated under reduced pressure. This crude material was purified by column chromatography on silica gel using a gradient of methanol-ethyl acetate to provide the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.93-2.03 (m, 1H), 2.1-2.17 (m, 1H), 3.23 (d, 1H, J=12.3 Hz), 3.55 (d, 1H, J=4.2 Hz), 3.63 (d, 1H, J=16.5 Hz), 4.15 (m, 1H), 4.32 (bs, 1H), 4.47-4.59 (m, 3H), 5.16 (s, 1H), 7.24-7.37 (m, 5H).

Workup

  1. temperatureThe reaction mixture was cooled
  2. concentrationconcentrated under reduced pressure
  3. customThis crude material was purified by column chromatography on silica gel using a gradient of methanol-ethyl acetate

Sources & evidence

ORD record
ord-7255d88fb7bf4ecbab6e361c42211792
Source dataset
uspto-grants-2014_03
Patent number
US08669255B2

Reaction notes

Loading…