Acetic Acid → HCID 178468707, compound

HRID 396385Notes

Reaction equation

HRID 396385 reaction equation
[C:1]1([C:7]2[S:8][C:9]([C:18](=O)[CH3:19])=[C:10]([N:12]3[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]3)[N:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CC(C)([O-])C.[K+].[C:27](OCC)(=O)[C:28]([O:30][CH2:31][CH3:32])=[O:29].C(O)(=O)C.O.[NH2:42][NH2:43]>C1COCC1.CCO.C(OCC)(=O)C>[CH2:31]([O:30][C:28]([C:27]1[NH:42][N:43]=[C:18]([C:9]2[S:8][C:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)=[N:11][C:10]=2[N:12]2[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]2)[CH:19]=1)=[O:29])[CH3:32]

Participants

9

Reactant 5

HCID 176Acetic AcidHCID 7268Diethyl OxalateHCID 24654Hydrazine hydrate (1:1)HCID 9900530HCID 9900530, compoundHCID 23665647Potassium tert-butoxide

Product 1

HCID 178468707HCID 178468707, compoundYield 59%

Reagents, catalysts & solvents 3

HCID 702EthanolSolvent2×HCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of the above-prepared 1-(2-phenyl-4-piperidin-1-yl-thiazol-5-yl)-ethanone (0.545 mmol) in dry THF (5 mL) was treated dropwise with a 1.0M potassium t-butoxide in THF solution (0.654 mmol). The suspension was stirred at room temperature under nitrogen for 15 minutes. Diethyl oxalate (0.600 mmol) was added, and the brown suspension was diluted with additional THF (6 mL) and allowed to stir at room temperature for 30 minutes. The reaction mixture was quenched by adding glacial acetic acid (0.710 mmol) and ethanol (5 mL). The solvent was removed in vacuo leaving a residual oil that was dissolved in absolute EtOH (5 mL). The ethanolic solution was treated with hydrazine monohydrate(0.655 mmol) and the mixture heated at 80° C. for 1 hour. The resulting yellow suspension was concentrated in vacuo leaving a residual oil that was dissolved in ethyl acetate. This organic phase was washed with water, saturated NaHCO3 and brine, then dried over MgSO4 and evaporated in vacuo to give a yellow oily solid. Silica gel chromatography provided the title compound (59%) as a yellow solid. 1H NMR(CDCl3): δ 1.4 (t, 3H), 1.6-1.9 (6H), 3.1 (m, 4H), 4.4 (q, 2H), 6.9 (broad s, 1H), 7.4-7.5 (m, 3H), 7.9 (m, 2H).

Workup

  1. stirringto stir at room temperature for 30 minutes
  2. customThe reaction mixture was quenched
  3. customThe solvent was removed in vacuo
  4. customleaving a residual oil that
  5. temperaturethe mixture heated at 80° C. for 1 hour
  6. concentrationThe resulting yellow suspension was concentrated in vacuo
  7. customleaving a residual oil that
  8. washThis organic phase was washed with water, saturated NaHCO3 and brine
  9. dry with materialdried over MgSO4
  10. customevaporated in vacuo
  11. customto give a yellow oily solid

Sources & evidence

ORD record
ord-42ed1b0af2924e94ae026630957f1d28
Source dataset
uspto-grants-2003_08
Patent number
US06608087B1

Reaction notes

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