Sodium hydride → (S)-3-(hydroxymethyl)-6a,7,8,9-tetrahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-6(5H)-one

HRID 2097781Notes

Reaction equation

HRID 2097781 reaction equation
[O:1]=[C:2]1[NH:7][C:6]2[CH:8]=[C:9]([C:12](OC)=[O:13])[CH:10]=[N:11][C:5]=2[N:4]2[CH2:16][CH2:17][CH2:18][C@@H:3]12.[H-].[Na+].[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[OH:13][CH2:12][C:9]1[CH:10]=[N:11][C:5]2[N:4]3[CH2:16][CH2:17][CH2:18][C@H:3]3[C:2](=[O:1])[NH:7][C:6]=2[CH:8]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 21226445Aluminium lithium hydrideHCID 58324449(S)-methyl6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazine-3-carboxylate

Product 1

HCID 58324378(S)-3-(hydroxymethyl)-6a,7,8,9-tetrahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-6(5H)-oneYield 112.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(S)-methyl 6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazine-3-carboxylate (3.00 g, 10.5 mmol) was suspended in THF and sodium hydride (60% suspension in mineral oil, 0.712 g, 17.8 mmol) was added under nitrogen atmosphere. The reaction mixture was stirred at room temperature for 1 h and cooled to −78° C. LiAlH4 (2M in THF, 12.5 mL, 25 mmol) was added dropwise over 5 min and the reaction mixture was allowed to warm to −40° C. and kept at −40-(−20)° C. for 3 h. The reaction mixture was cooled to −60° C. and quenched with MeOH, water and TFA until a clear mixture resulted. This was purified using HPLC (1-30% acetnitrile in water, TFA buffered). The fractions containing product were concentrated in vacuo and crystallized with ethyl ether. The solid was filtered and dried in vacuum to afford the title compound as a grey solid (2.60 g, 74%, TFA salt). [M+H] calc'd for C11H13N3O2, 220; found, 220.

Workup

  1. temperaturecooled to −78° C
  2. temperatureto warm to −40° C.
  3. waitfor 3 h
  4. temperatureThe reaction mixture was cooled to −60° C.
  5. customquenched with MeOH, water and TFA until a clear mixture
  6. customresulted
  7. customThis was purified
  8. additionThe fractions containing product
  9. concentrationwere concentrated in vacuo
  10. customcrystallized with ethyl ether
  11. filtrationThe solid was filtered
  12. customdried in vacuum

Sources & evidence

ORD record
ord-557a83c3cce143f4b3c79845defa40ec
Source dataset
uspto-grants-2013_05
Patent number
US08450323B2

Reaction notes

Loading…