Triethylamine → 6-Cyclobutylmethoxy-5-pyrrolidin-1-yl-pyrazine-2-carboxylic acid methyl ester

HRID 639300Notes

Reaction equation

HRID 639300 reaction equation
Br[C:2]1[N:3]=[C:4]([O:13][CH2:14][CH:15]2[CH2:18][CH2:17][CH2:16]2)[C:5]([N:8]2[CH2:12][CH2:11][CH2:10][CH2:9]2)=[N:6][CH:7]=1.[C:19]([O:22][CH2:23]C)(=[O:21])C.C(N(CC)CC)C>CO>[CH3:23][O:22][C:19]([C:2]1[CH:7]=[N:6][C:5]([N:8]2[CH2:12][CH2:11][CH2:10][CH2:9]2)=[C:4]([O:13][CH2:14][CH:15]2[CH2:18][CH2:17][CH2:16]2)[N:3]=1)=[O:21]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 866195185-Bromo-3-cyclobutylmethoxy-2-pyrrolidin-1-yl-pyrazine

Product 1

HCID 685689986-Cyclobutylmethoxy-5-pyrrolidin-1-yl-pyrazine-2-carboxylic acid methyl esterYield 75%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
100 °C

Procedure

A 50 mL bomb with a glass liner was charged with the 5-bromo-3-cyclobutylmethoxy-2-pyrrolidin-1-yl-pyrazine (2.27 g, 7.3 mmol), ethyl acetate (6 mL, degassed), methanol (7 mL, degassed) and triethylamine (2.0 mL, 14.5 mmol). PdCl2dppfCH2Cl2 (0.29 g, 0.36 mmol) was charged to the bomb; the bomb was sealed and degassed under vacuum. The reaction was purged with carbon monoxide (×5) then pressurized to 5 bar and heated to 100° C. for 1 hour. The reaction mixture was filtered through celite and washed with methanol then ethyl acetate and the filtrate was concentrated in vacuo. The residue was dissolved in ethyl acetate (100 mL) and washed with water (100 mL) the organic layer was dried over MgSO4 and concentrated in vacuo to afford 6-cyclobutylmethoxy-5-pyrrolidin-1-yl-pyrazine-2-carboxylic acid methyl ester as an orange solid, 2.2 g (75% yield). LC@215 nm; Rt 2.39: 75%, m/z (ES+): 292 (M+H).

Workup

  1. additionPdCl2dppfCH2Cl2 (0.29 g, 0.36 mmol) was charged to the bomb
  2. customthe bomb was sealed
  3. customdegassed under vacuum
  4. customThe reaction was purged with carbon monoxide (×5)
  5. filtrationThe reaction mixture was filtered through celite
  6. washwashed with methanol
  7. concentrationethyl acetate and the filtrate was concentrated in vacuo
  8. dissolutionThe residue was dissolved in ethyl acetate (100 mL)
  9. washwashed with water (100 mL) the organic layer
  10. dry with materialwas dried over MgSO4
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-91c218920ec1415792b9c26af2571eca
Source dataset
uspto-grants-2010_04
Patent number
US07691863B2

Reaction notes

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