Lithium diisopropylamide → HCID 67168837, compound

HRID 1506363Notes

Reaction equation

HRID 1506363 reaction equation
[Li+].CC([N-]C(C)C)C.[CH:9]([C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[C:17](=[O:21])[CH2:16][CH2:15][CH2:14]2)=[CH2:10].[C:22]1([C:28]2[C:32]([C:33]([F:36])([F:35])[F:34])=[C:31]([C:37](F)=[O:38])[O:30][N:29]=2)[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>C1COCC1>[C:22]1([C:28]2[C:32]([C:33]([F:36])([F:34])[F:35])=[C:31]([C:37]([CH:16]3[CH2:15][CH2:14][C:13]4[C:18](=[CH:19][CH:20]=[C:11]([CH:9]=[CH2:10])[CH:12]=4)[C:17]3=[O:21])=[O:38])[O:30][N:29]=2)[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

Participants

5

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 58374067HCID 58374067, compound2×HCID 67167908HCID 67167908, compound

Product 1

HCID 67168837HCID 67168837, compoundYield 35%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

The LDA solution was cooled to −78° C. and 6-vinyl-3,4-dihydronaphthalen-1(2H)-one (Intermediate I-1B, 0.299 g, 1.736 mmol) dissolved in 1 mL of THF was added dropwise over a period of 2 min. The pale yellow reaction mixture was stirred at −78° C. for 20 min. Then, 3-phenyl-4-(trifluoromethyl)isoxazole-5-carbonyl fluoride (Intermediate 4, 0.450 g, 1.736 mmol) dissolved in 1 mL of THF was added dropwise over a period of 2 min. The reaction mixture was stirred at −78° C. for 20 min, brought to room temperature, and stirred at room temperature for 10 min. The reaction mixture was quenched with 1N hydrochloric acid (5 mL) and extracted into ethyl acetate (20 mL). The aqueous layer was re-extracted with ethyl acetate (10 mL). The combined organic layers were dried over sodium sulfate, concentrated, and purified by silica gel column chromatography (hexane/ethyl acetate). Fractions corresponding to the product were collected and concentrated to yield 2-(3-phenyl-4-(trifluoromethyl)isoxazole-5-carbonyl)-6-vinyl-3,4-dihydronaphthalen-1(2H)-one (0.25 g, 0.608 mmol, 35.0% yield) as a yellow solid. LC/MS M+1=412.1.

Workup

  1. additionwas added dropwise over a period of 2 min
  2. additionwas added dropwise over a period of 2 min
  3. stirringThe reaction mixture was stirred at −78° C. for 20 min
  4. custombrought to room temperature
  5. stirringstirred at room temperature for 10 min
  6. customThe reaction mixture was quenched with 1N hydrochloric acid (5 mL)
  7. extractionextracted into ethyl acetate (20 mL)
  8. extractionThe aqueous layer was re-extracted with ethyl acetate (10 mL)
  9. dry with materialThe combined organic layers were dried over sodium sulfate
  10. concentrationconcentrated
  11. custompurified by silica gel column chromatography (hexane/ethyl acetate)
  12. customFractions corresponding to the product were collected
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-09f4ec6fc13e4d00ae1ac596b2fd7f72
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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