Acetic Acid → HCID 14699194, compound

HRID 359464Notes

Reaction equation

HRID 359464 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[C:13]([O:19][CH3:20])(=[O:18])[CH2:14][C:15]([CH3:17])=[O:16].[F:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2[CH:37]=[C:36]([C:38]3[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=3)[CH2:35][C:30]3([CH2:34][CH2:33][CH2:32][CH2:31]3)[C:29]=2/[CH:45]=[CH:46]/[CH:47]=[O:48])=[CH:24][CH:23]=1.C(O)(=O)C>C1COCC1.C(OC(=O)C)C.CCCCCC>[CH3:20][O:19][C:13](=[O:18])[CH2:14][C:15](=[O:16])[CH2:17][CH:47]([OH:48])/[CH:46]=[CH:45]/[C:29]1[C:30]2([CH2:35][C:36]([C:38]3[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=3)=[CH:37][C:28]=1[C:25]1[CH:24]=[CH:23][C:22]([F:21])=[CH:27][CH:26]=1)[CH2:34][CH2:33][CH2:32][CH2:31]2

Participants

9

Reactant 5

HCID 176Acetic AcidHCID 7757Methyl acetoacetateHCID 7912DiisopropylamineHCID 14699193HCID 14699193, compoundHCID 178418339Butyllithium

Product 1

HCID 14699194HCID 14699194, compoundYield 93.4%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent4×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of diisopropylamine (3.13 ml, 22.38 mmoles) in 80 ml of anhydrous THF at -78° C., under nitrogen, was added 8.24 ml (20.59 mmoles) of a 2.5M hexane solution of n-butyllithium. After stirring for 5 minutes, a solution of methyl acetoacetate (1.07 g, 9.19 mmoles) in 10 ml of THF was added dropwise over 15 minutes. The dry ice acetone bath was removed and, after 10 minutes, an ice bath was applied. The mixture was stirred for 1.5 hours. To this mixture was added a solution of (E)-3-[7,9-di-(4-fluorophenyl)spiro[4.5]deca-6,8-dien-6-yl]2-propenaldehyde (2.7 g, 7.17 mmoles) in 50 ml of THF dropwise over 40 minutes. The mixture was stirred in ice for 1 hour and a solution of glacial acetic acid (2.46 ml, 42.97 mmoles) in 10 ml of THF was added dropwise over 5 minutes. The mixture was poured into 250 ml of ethylacetate and was extracted with water, sodium bicarbonate and brine. The organic layer was dried over magnesium sulfate and was evaporated in vacuo to give 3.3 g of product having an m.p. of 96-9° C.

Workup

  1. customThe dry ice acetone bath was removed and, after 10 minutes
  2. customan ice bath was applied
  3. stirringThe mixture was stirred for 1.5 hours
  4. stirringThe mixture was stirred in ice for 1 hour
  5. extractionwas extracted with water, sodium bicarbonate and brine
  6. dry with materialThe organic layer was dried over magnesium sulfate
  7. customwas evaporated in vacuo

Sources & evidence

ORD record
ord-d1b12b09b43b4ac2be0104ecf70150bd
Source dataset
uspto-grants-1991_03
Patent number
US05001128

Reaction notes

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