Acetic Acid → HCID 59556734, compound

HRID 1172958Notes

Reaction equation

HRID 1172958 reaction equation
I[C:2]1[N:3]=[C:4]2[CH2:9][N:8]([C:10]([O:12][CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[O:11])[CH2:7][CH2:6][N:5]2[C:20]=1[CH3:21].C([Mg]Br)C.[C:26]([OH:29])(=[O:28])C>C1COCC1>[CH2:13]([O:12][C:10]([N:8]1[CH2:7][CH2:6][N:5]2[C:20]([CH3:21])=[C:2]([C:26]([OH:29])=[O:28])[N:3]=[C:4]2[CH2:9]1)=[O:11])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 59556567HCID 59556567, compoundHCID 178418443HCID 178418443, compound

Product 1

HCID 59556734HCID 59556734, compoundYield 52.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of benzyl 2-iodo-3-methyl-5,6-dihydroimidazo[1,2-a]pyrazine-7(8H)-carboxylate (900mg, 2.266 mmol) in dry THF (25 ml) was cooled to 0 ° C. and ethyl magnesiumbromide (1.888 ml, 5.66 mmol) was added at such a rate as to maintain the reaction temperature below 2.5° C. The reaction was stirred under Nitrogen at 0 ° C. for 15 minutes, then the reaction was quenched with a stream of carbon dioxide. The reaction was concentrated to solids and acetic acid (0.60 ml, 10.48 mmol) ethyl acetate (50 ml) were added and the suspension was stirred vigorously at room temperature for 15 minutes. The resulting solid was filtered and washed with an additional 15 ml ethyl acetate. The residue was dissolved in 10 ml water plus 2N HCl to pH 4, then washed 2 times 10 ml ether then extract with 4×20 ml CH2Cl2. Dry the combined organic extracts over sodium sulfate, filtered and dried under reduced pressure to yield 3-Methy-5,6-dihydro -8H-imidazo[1,2-a] pyrazine-2,7-dicarboxylic acid 7-benzyl ester (374 mg, 52%) as a foam. LCMS (Table 1, Method a) Rt=2.28 min, m/z 316.10 (M+H)+; 1H NMR (400 MHz, DMSO-d6)δ 7.35 (m, 5H), 5.11 (s, 2H), 4.56 (s,broad, 2H), 3.88 (m, 2H), 3.83 (s, broad, 2H), 2.36 (s, 3H).

Workup

  1. temperatureto maintain the reaction temperature below 2.5° C
  2. customthe reaction was quenched with a stream of carbon dioxide
  3. additionwere added
  4. stirringthe suspension was stirred vigorously at room temperature for 15 minutes
  5. filtrationThe resulting solid was filtered
  6. washwashed with an additional 15 ml ethyl acetate
  7. dissolutionThe residue was dissolved in 10 ml water
  8. wash2N HCl to pH 4, then washed 2 times 10 ml ether
  9. extractionthen extract with 4×20 ml CH2Cl2
  10. dry with materialDry the combined organic extracts over sodium sulfate
  11. filtrationfiltered
  12. customdried under reduced pressure

Sources & evidence

ORD record
ord-782ad40aad124a1bb8e46b8add9f9ec1
Source dataset
uspto-grants-2010_11
Patent number
US07834039B2

Reaction notes

Loading…