Diisopropylamine → HCID 67167591、化合物

HRID 1506472ノート

反応式

HRID 1506472 の反応式
C(NC(C)C)(C)C.[Li]CCCC.[CH:13]([C:15]1[CH:16]=[C:17]2[C:22](=[CH:23][CH:24]=1)[C:21](=[O:25])[CH2:20][CH2:19][CH2:18]2)=[CH2:14].[C:26]1([C:32]2[O:36][N:35]=[C:34]([C:37](F)=[O:38])[C:33]=2[C:40]([F:43])([F:42])[F:41])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>C1COCC1>[C:26]1([C:32]2[O:36][N:35]=[C:34]([C:37]([CH:20]3[CH2:19][CH2:18][C:17]4[C:22](=[CH:23][CH:24]=[C:15]([CH:13]=[CH2:14])[CH:16]=4)[C:21]3=[O:25])=[O:38])[C:33]=2[C:40]([F:42])([F:43])[F:41])[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1

参加物

6

反応物 4

HCID 7912DiisopropylamineHCID 58374105HCID 58374105、化合物HCID 67167908HCID 67167908、化合物HCID 178418339Butyllithium

生成物 1

HCID 67167591HCID 67167591、化合物収率 64.9%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒3 回

反応条件

温度
0 °C

実験手順

To a heat gun dried 100 mL 2-necked flask was added diisopropylamine (0.910 mL, 6.39 mmol) under a nitrogen atmosphere followed by THF (5 mL). The flask was cooled to 0° C. and n-BuLi (2.55 mL, 6.39 mmol) was added dropwise over a period of 2 min. The contents were stirred at 0° C. for 20 min., cooled to −78° C. and 6-vinyl-3,4-dihydronaphthalen-1(2H)-one (I-1B, 1 g, 5.81 mmol) dissolved in 2 mL of THF was added dropwise over a period of 3 min. The pale yellow reaction mixture was stirred at −78° C. for 20 min. Then 5-phenyl-4-(trifluoromethyl)isoxazole-3-carbonyl fluoride (I-14, 1.505 g, 5.81 mmol) dissolved in 2 mL of THF was added dropwise over a period of 2 min. The reaction mixture was stirred at −78° C. for 20 min, bought to room temperature and stirred at room temperature for 10 min. The reaction mixture was quenched with 1N HCl (5 mL) and extracted into EtOAc (20 mL). The aqueous layer was re-extracted with EtOAc (10 mL). The combined organic layers were dried over sodium sulfate concentrated and purified by column chromatography using an ISCO setup (80 g, RediSep® silica gel column). The desired fractions were collected and concentrated to yield 2-(5-phenyl-4-(trifluoromethyl)isoxazole-3-carbonyl)-6-vinyl-3,4-dihydronaphthalen-1(2H)-one (1.55 g, 3.77 mmol, 64.9% yield) as a yellow solid. LC/MS M+1=412.12.

後処理

  1. customTo a heat gun dried 100 mL 2-necked flask
  2. temperaturecooled to −78° C.
  3. additionwas added dropwise over a period of 3 min
  4. stirringThe pale yellow reaction mixture was stirred at −78° C. for 20 min
  5. additionwas added dropwise over a period of 2 min
  6. stirringThe reaction mixture was stirred at −78° C. for 20 min
  7. custombought to room temperature
  8. stirringstirred at room temperature for 10 min
  9. customThe reaction mixture was quenched with 1N HCl (5 mL)
  10. extractionextracted into EtOAc (20 mL)
  11. extractionThe aqueous layer was re-extracted with EtOAc (10 mL)
  12. dry with materialThe combined organic layers were dried over sodium sulfate
  13. concentrationconcentrated
  14. custompurified by column chromatography
  15. customThe desired fractions were collected
  16. concentrationconcentrated

出典と根拠

ORDレコード
ord-d78b9821094c4bd2a5a2ae8d5534af07
出典データセット
uspto-grants-2015_12
特許番号
US09216972B2

反応ノート

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