Lithium diisopropylamide → HCID 67168837, 화합물

HRID 1506363노트

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HRID 1506363 반응식
[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

참가 물질

5

반응물 3

HCID 2724682Lithium diisopropylamideHCID 58374067HCID 58374067, 화합물2회HCID 67167908HCID 67167908, 화합물

생성물 1

HCID 67168837HCID 67168837, 화합물수율 35%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

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온도
-78 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-09f4ec6fc13e4d00ae1ac596b2fd7f72
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09216972B2

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