3-Ethoxycyclohex-2-ene-1-one → HCID 67322634, compound

HRID 1257583Notes

Reaction equation

HRID 1257583 reaction equation
C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[CH2:11]([O:13][C:14]1[CH2:19][CH2:18][CH2:17][C:16](=[O:20])[CH:15]=1)[CH3:12].CN1CCCN(C)C1=O.[CH3:30][O:31][C:32]1[CH:43]=[C:42]([O:44][CH3:45])[CH:41]=[CH:40][C:33]=1[CH2:34][NH:35][C:36](=[O:39])[CH2:37]I>C1COCC1>[CH3:30][O:31][C:32]1[CH:43]=[C:42]([O:44][CH3:45])[CH:41]=[CH:40][C:33]=1[CH2:34][NH:35][C:36](=[O:39])[CH2:37][CH:17]1[CH2:18][CH2:19][C:14]([O:13][CH2:11][CH3:12])=[CH:15][C:16]1=[O:20]

Participants

6

Reactant 4

HCID 792163-Ethoxycyclohex-2-ene-1-oneHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-HCID 2733832Lithium HexamethyldisilazideHCID 67324610HCID 67324610, compound

Product 1

HCID 67322634HCID 67322634, compoundYield 56%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

To a −78° C. solution of 1.0 M lithium hexamethyldisilazide in THF (0.90 mL) in 4.0 mL THF was added 3-ethoxy-2-cyclohexen-1-one (0.100 mL, 0.687 mmol). After stirring at −78° C. for 40 minutes, 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (1.0 mL, 8.3 mmol) was added. After 5 minutes, N-(2,4-Dimethoxy-benzyl)-2-iodo-acetamide (0.342 g, 1.02 mmol) was added as a solution in 2.0 mL THF. The reaction was kept at −78° C. for one hour, and then quenched with water and partitioned between ethyl acetate and water. The organic layer was dried over magnesium sulfate, filtered, and evaporated in vacuo. Purification by column chromatography on silica gel (gradient: 0 to 100% ethyl acetate in dichloromethane) yielded 133.5 mg (56%) of N-(2,4-dimethoxy-benzyl)-2-(4-ethoxy-2-oxo-cyclohex-3-enyl)-acetamide. LCMS (Method E, ESI): RT=1.57 min, m+H=336.2; 1H NMR (400 MHz, CDCl3) δ: 7.17 (d, J=8.1 Hz, 1H), 6.47-6.39 (m, 2H), 6.35 (s, 1H), 5.32 (s, 1H), 4.38-4.30 (m, 2H), 3.90 (dd, J=13.5, 6.5 Hz, 2H), 3.82 (s, 3H), 3.79 (s, 3H), 2.77 (dd, J=14.3, 5.6 Hz, 1H), 2.68 (dt, J=10.6, 5.5 Hz, 1H), 2.59-2.48 (m, 1H), 2.37 (ddd, J=12.0, 6.3, 2.9 Hz, 1H), 2.17 (ddd, J=13.1, 11.2, 4.6 Hz, 2H), 1.72 (ddd, J=25.0, 12.6, 4.9 Hz, 1H), 1.36 (t, J=7.0 Hz, 3H).

Workup

  1. waitAfter 5 minutes
  2. waitThe reaction was kept at −78° C. for one hour
  3. customquenched with water
  4. custompartitioned between ethyl acetate and water
  5. dry with materialThe organic layer was dried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customPurification by column chromatography on silica gel (gradient: 0 to 100% ethyl acetate in dichloromethane)

Sources & evidence

ORD record
ord-ac128dd18aaa4ba1b7046e6abb54ec4e
Source dataset
uspto-grants-2013_06
Patent number
US08461328B2

Reaction notes

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