Acetic Acid → HCID 59142065, compound

HRID 1810943Notes

Reaction equation

HRID 1810943 reaction equation
[CH3:1][O:2][C:3]1[C@H:4]([CH:11]([CH3:13])[CH3:12])[N:5]=[C:6]([O:9][CH3:10])[CH2:7][N:8]=1.C([Li])C[CH2:16][CH3:17].[PH:19](=[O:29])([O-:28])[O:20][CH2:21][C:22](CC)(CC)Br.[C:30](O)(=O)[CH3:31]>C1COCC1>[CH2:30]([O:28][P:19]([CH2:16][CH2:17][C@@H:7]1[C:6]([O:9][CH3:10])=[N:5][C@@H:4]([CH:11]([CH3:13])[CH3:12])[C:3]([O:2][CH3:1])=[N:8]1)([O:20][CH2:21][CH3:22])=[O:29])[CH3:31]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 736065(2S)-2,5-Dihydro-2-isopropyl-3,6-dimethoxypyrazineHCID 178418339ButyllithiumHCID 178438280HCID 178438280, compound

Product 1

HCID 59142065HCID 59142065, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

0.52 mol of (S)-2,5-dihydro-3,6-dimethoxy-2-isopropyl pyrazine are solved in 400 ml of absolute THF under argon and are cooled to −78° C. Under stirring, 200 ml of a 2.7 M solution of butyl lithium (in heptane) (0.54 mol) are added in drops and slowly. Subsequently, a solution of 0.52 mol diethyl-(2-bromethyl) phosphonate in 300 ml of absolute THF is added in drops and slowly during stirring, and the mixture is stirred for further 3 h at −78° C. Then, 11.7 ml (about 0.2 mol) anhydrous acetic acid are added slowly. The reaction mixture is allowed to warm up slowly to room temperature. The solvent is removed, and the residue is solved in 600 ml of diethyl ether and washed with 200 ml of water. The aqueous phase is still extracted three times with each 100 ml of diethyl ether. The combined ether phases are dried over MgSO4, filtered and the solvent is removed in vacuo. The residue is solved in a mixture of diethyl ether and hexane (1:10) and filtered over a bed of silica gel. Thereafter, the non reacted educt is eluted with diethyl ether and hexane (1:5). Finally, the product is eluted with acetic acid ethyl ester.

Workup

  1. stirringslowly during stirring
  2. stirringthe mixture is stirred for further 3 h at −78° C
  3. temperatureto warm up slowly to room temperature
  4. customThe solvent is removed
  5. washwashed with 200 ml of water
  6. extractionThe aqueous phase is still extracted three times with each 100 ml of diethyl ether
  7. dry with materialThe combined ether phases are dried over MgSO4
  8. filtrationfiltered
  9. customthe solvent is removed in vacuo
  10. additionThe residue is solved in a mixture of diethyl ether and hexane (1:10)
  11. filtrationfiltered over a bed of silica gel
  12. washThereafter, the non reacted educt is eluted with diethyl ether and hexane (1:5)
  13. washFinally, the product is eluted with acetic acid ethyl ester

Sources & evidence

ORD record
ord-f15639b943d846f38a8e1882d149b096
Source dataset
uspto-grants-2013_01
Patent number
US08362243B2

Reaction notes

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