Diethyl Oxalate → HCID 54692280, compound

HRID 1162831Notes

Reaction equation

HRID 1162831 reaction equation
[CH:1]([NH:4][C:5]([N:7]1[CH2:12][C:11](=[O:13])[N:10]2[CH:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:15][CH2:16][CH:9]2[CH2:8]1)=[O:6])([CH3:3])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C1COCC1.[C:38](OCC)(=[O:44])[C:39](OCC)=[O:40]>CN(C=O)C>[OH:44][C:38]1[C:39](=[O:40])[N:4]([CH:1]([CH3:3])[CH3:2])[C:5](=[O:6])[N:7]2[CH2:8][C@@H:9]3[CH2:16][CH2:15][C@H:14]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)[N:10]3[C:11](=[O:13])[C:12]=12

Participants

6

Reactant 4

HCID 7268Diethyl OxalateHCID 8028Tetrahydrofuran2×HCID 2733832Lithium Hexamethyldisilazide2×HCID 77497993HCID 77497993, compound

Product 1

HCID 54692280HCID 54692280, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of racemic (6R,8aS)-N-isopropyl-4-oxo-6-phenylhexahydropyrrolo[1,2-a]pyrazine-2(1H)-carboxamide (0.187 g, 0.620 mmol) in DMF (3 mL) at 0° C. was added a 1M solution of lithium bis(trimethylsilyl)amide in THF (1.49 mL, 1.49 mmol), followed by diethyl oxalate (0.101 mL, 0.745 mmol). The mixture was stirred for 18 h, allowing the cooling bath to warm to ambient temperature. The resultant mixture was then treated with additional lithium bis(trimethylsilyl)amide in THF (1.49 mL, 1.49 mmol) and stirred at room temperature for 6 h. The product mixture was concentrated under vacuum and the residue was partitioned between aqueous HCl and ethyl acetate. The organic extract was concentrated under vacuum. The residue was subjected to HPLC purification on C18 stationary phase eluted with water/acetonitrile/TFA mobile phase to give the title compound as a solid. HPLC RT=3.19 min, 95% at 215 nm (Method A); ES MS (M+H)=356.2; 1H NMR (400 MHz, DMSO-d6) δ 7.32-7.24 (m, 2H) 7.22-7.16 (m, 3H) 5.12-5.02 (m, 2H) 4.80-4.74 (d, 1H) 3.84-3.74 (m, 1H) 2.38-2.28 (m, 1H) 2.06-1.98 (m, 1H) 1.74-1.66 (m, 1H) 1.42-1.34 (dd, 6H) 1.34-1.26 (m, 1H).

Workup

  1. stirringstirred at room temperature for 6 h
  2. concentrationThe product mixture was concentrated under vacuum
  3. customthe residue was partitioned between aqueous HCl and ethyl acetate
  4. extractionThe organic extract
  5. concentrationwas concentrated under vacuum
  6. customThe residue was subjected to HPLC purification on C18 stationary phase
  7. washeluted with water/acetonitrile/TFA mobile phase

Sources & evidence

ORD record
ord-9ea55a4f57204a8487f76228fe05b2bc
Source dataset
uspto-grants-2010_10
Patent number
US07820680B2

Reaction notes

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