Methyl acetoacetate → HCID 54682268, compound

HRID 356488Notes

Reaction equation

HRID 356488 reaction equation
[C:1](OC)(=[O:6])[CH2:2][C:3]([CH3:5])=[O:4].[H-].[Na+].C([Li])CCC.[O:16]=[C:17]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH2:18][CH2:19][C:20]1[CH:25]=[CH:24][C:23]([NH:26][C:27](=[O:29])[CH3:28])=[CH:22][CH:21]=1>C1COCC1.O>[OH:4][C:3]1[CH2:5][C:17]([CH2:18][CH2:19][C:20]2[CH:25]=[CH:24][C:23]([NH:26][C:27](=[O:29])[CH3:28])=[CH:22][CH:21]=2)([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[O:16][C:1](=[O:6])[CH:2]=1

Participants

7

Reactant 4

HCID 7757Methyl acetoacetateHCID 24758Sodium hydrideHCID 18798652N-[4-(3-Oxo-3-phenylpropyl)phenyl]acetamideHCID 178418339Butyllithium

Product 1

HCID 54682268HCID 54682268, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Methyl acetoacetate (4.5 mL, 41.7 mmol) was added dropwise to a slurry of 60% sodium hydride (1.75 g, 43.7 mmol) in THF (135 mL) at 0° C. After stirring 15 minutes, n-butyllithium (21 mL of 2.1M, 44.1 mmol) was added and the reaction stirred an additional 15 minutes at 0° C. N-[4-(3-Oxo-3-phenyl-propyl)-phenyl]-acetamide, prepared in Example Y (5.3 g, 19.8 mmol) in THF (15 mL) was added in one portion and the reaction allowed to warm to room temperature over 4 hours. H2O was added and the reaction allowed to stir overnight. The mixture was extracted with Et2O and the aqueous layer acidified with 1N HCl. The precipitate was filtered, then washed with EtOAc to give the title compound, m.p. 155°-160° C. 1H NMR (DMSO-d6) δ 2.0 (s, 3 H), 2.17 (m, 2 H), 2.50 (m, 2 H), 3.02 (dd, 2 H), 4.88 (s, 1 H), 6.99 (d, 2 H), 7.25-7.50 (m, 7 H), 9.81 (s, 1 H), 11.50 (s, 1 H).

Workup

  1. stirringthe reaction stirred an additional 15 minutes at 0° C
  2. additionwas added in one portion
  3. stirringto stir overnight
  4. extractionThe mixture was extracted with Et2O
  5. filtrationThe precipitate was filtered
  6. washwashed with EtOAc

Sources & evidence

ORD record
ord-09522bbd59d6484c86f55c603314e8e2
Source dataset
uspto-grants-1998_11
Patent number
US05834506

Reaction notes

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