Potassium tert-butoxide → tert-Butyl 5-ethyl-7,8-dihydropyrido[3,4-b]pyrazine-6(5H)-carboxylate

HRID 132867Notes

Reaction equation

HRID 132867 reaction equation
[CH3:1][C:2]([CH3:5])([O-:4])[CH3:3].[K+].[CH2:7]([CH:9]1[C:14]2=[N:15][CH:16]=[CH:17][N:18]=[C:13]2[CH2:12][CH2:11][N:10]1[C:19](OC1C=CC=CC=1)=[O:20])[CH3:8]>O1CCCC1>[CH2:7]([CH:9]1[C:14]2=[N:15][CH:16]=[CH:17][N:18]=[C:13]2[CH2:12][CH2:11][N:10]1[C:19]([O:4][C:2]([CH3:5])([CH3:3])[CH3:1])=[O:20])[CH3:8]

Participants

4

Reactant 2

HCID 23665647Potassium tert-butoxideHCID 69182558Phenyl 5-ethyl-7,8-dihydropyrido[3,4-b]pyrazine-6(5H)-carboxylate

Product 1

HCID 69184558tert-Butyl 5-ethyl-7,8-dihydropyrido[3,4-b]pyrazine-6(5H)-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-25 °C

Procedure

Potassium tert-butoxide (11.0M in tetrahydrofuran, 0.7 mL, 0.7 mmol) was added over 3 min to a solution of phenyl 5-ethyl-7,8-dihydropyrido[3,4-b]pyrazine-6(5H)-carboxylate (91 mg, 0.32 mmol) in tetrahydrofuran (1.8 mL) cooled in a −20 to −30° C. bath. After 30 min, the bath was removed and stirring was continued for 75 min. The mixture was added to saturated aqueous sodium bicarbonate solution (10 mL) which was then extracted with two portions of ethyl acetate (35 mL and 15 mL). The organic layers were washed in succession with saturated aqueous brine (10 mL), dried over sodium sulfate, decanted, and evaporated. Purification by flash column chromatography (silica gel, 15% ethyl acetate/hexanes) gave the title compound as a colorless oil. 1H NMR (500 MHz, CD3OD) δ 8.43 (d, 1H, J=2 Hz), 8.40 (d, 1H, J=2 Hz), 5.17-5.02 (bm, 1H), 4.40-4.25 (bm, 1H), 3.37-3.20 (bm, 1H), 3.04 (ddd, 1H, J=17, 12, 6 Hz), 2.90 (dd, 1H, J=17, 4 Hz), 2.10-2.00 (m, 1H), 1.87-1.76 (m, 1H), 1.49 (s, 9H), 1.04 (bt, 3H). LC/MS 208 (M+1-56).

Workup

  1. customthe bath was removed
  2. waitwas continued for 75 min
  3. additionThe mixture was added to saturated aqueous sodium bicarbonate solution (10 mL) which
  4. extractionwas then extracted with two portions of ethyl acetate (35 mL and 15 mL)
  5. washThe organic layers were washed in succession with saturated aqueous brine (10 mL)
  6. dry with materialdried over sodium sulfate
  7. customdecanted
  8. customevaporated
  9. customPurification by flash column chromatography (silica gel, 15% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-f3997b5b3f1e43d3af4130f7e8fce403
Source dataset
uspto-grants-2008_06
Patent number
US07388019B2

Reaction notes

Loading…