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Diisopropylamine → (R)-N-((1S,2S)-1-(3-bromopyrazin-2-yl)-2-(2,3-difluorophenyl)hex-5-enyl)-2-methylpropane-2-sulfinamide

HRID 403340
ノート
印刷プレビュー

反応式

HRID 403340 の反応式
C(NC(C)C)(C)C.[Li]CCCC.[Br:13][C:14]1[CH:19]=[N:18][CH:17]=[CH:16][N:15]=1.[F:20][C:21]1[C:26]([F:27])=[CH:25][CH:24]=[CH:23][C:22]=1[C@H:28]([CH2:37][CH2:38][CH:39]=[CH2:40])/[CH:29]=[N:30]/[S@@:31]([C:33]([CH3:36])([CH3:35])[CH3:34])=[O:32]>O1CCCC1.C(OCC)(=O)C.CCCCCC>[Br:13][C:14]1[C:19]([C@@H:29]([NH:30][S@@:31]([C:33]([CH3:36])([CH3:35])[CH3:34])=[O:32])[C@H:28]([C:22]2[CH:23]=[CH:24][CH:25]=[C:26]([F:27])[C:21]=2[F:20])[CH2:37][CH2:38][CH:39]=[CH2:40])=[N:18][CH:17]=[CH:16][N:15]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 7912DiisopropylamineHCID 6428002-BromopyrazineHCID 89158770(NE,R)-N-[(2S)-2-(2,3-difluorophenyl)hex-5-enylidene]-2-methylpropane-2-sulfinamideHCID 178418339Butyllithium

生成物 1

HCID 86681334(R)-N-((1S,2S)-1-(3-bromopyrazin-2-yl)-2-(2,3-difluorophenyl)hex-5-enyl)-2-methylpropane-2-sulfinamide収率 62.3%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒2 回HCID 21226206Ethyl acetate hexane溶媒

反応条件

温度
-30 °C

実験手順

In an oven-dried 250 mL round-bottomed flask was dissolved diisopropylamine (1.7 mL, 12 mmol) in tetrahydrofuran (40 mL) to give a colorless solution under nitrogen. After cooling to −30° C., n-BuLi (4.3 mL, 11 mmol) was added, and the mixture was briefly warmed up to rt for 3 min. After cooling down to −78° C., 2-bromopyrazine (0.98 mL, 10.7 mmol) was added dropwise via syringe. The resulting yellow solution was stirred at −78° C. for 5 min. (R,E)-N—((S)-2-(2,3-difluorophenyl)hex-5-enylidene)-2-methylpropane-2-sulfinamide (2.089 g, 6.67 mmol) in 4 mL anhydrous tetrahydrofuran (plus 3 mL rinse) was added via canuula, and the mixture was stirred for 2 h at −75° C. The reaction was quenched with saturated sodium bicarbonate solution and diluted with ethyl acetate. The layers were separated. The aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried, and concentrated to give a tan oil. Flash column chromatography up to 80% ethyl acetate/hexane afforded the desired product (1.964 g, 62%) as a dense tan oil: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.33 (d, J=2.26 Hz, 1H) 8.26 (d, J=2.26 Hz, 1H) 6.99-7.22 (m, 3H) 5.74 (d, J=6.53 Hz, 1H) 5.18 (dd, J=9.29, 5.27 Hz, 1H) 4.85-4.99 (m, 2H) 4.30 (d, J=9.54 Hz, 1H) 3.66-3.77 (m, 1H) 2.17 (br. s., 1H) 1.80-2.04 (m, 3H) 1.05 (s, 9H); 19F NMR (376 MHz, CHLOROFORM-d) δ ppm −138.41 (d, J=15.61 Hz, 1F) −144.20-−143.20 (m, 1F); 13C NMR (101 MHz, CHLOROFORM-d) δ ppm 155.19 (s, 1C) 151.32-149.72 (dd, J=13.87 and 249.47 Hz, 1C) 150.24-147.67 (dd, J=12.72 and 246.95 Hz, 1C) 142.89 (s, 1C) 141.44 (br. s., 1C) 140.47 (s, 1C) 136.93 (d, J=10.02 Hz, 1C) 127.54 (d, J=10.79 Hz, 1C) 124.12-124.96 (m, 1C) 123.41-123.97 (m, 1C) 115.23-115.83 (m, 1C) 115.09 (s, 1C) 59.93-60.56 (m, 1C) 56.10-56.69 (m, 1C) 40.72-41.81 (m, 1C) 30.81 (s, 1C) 30.34 (br. s., 1C) 21.94 (q, J=6.17 Hz, 3C).

後処理

  1. customto give a colorless solution under nitrogen
  2. temperaturethe mixture was briefly warmed up to rt for 3 min
  3. temperatureAfter cooling down to −78° C.
  4. additionwas added via canuula
  5. stirringthe mixture was stirred for 2 h at −75° C
  6. customThe reaction was quenched with saturated sodium bicarbonate solution
  7. additiondiluted with ethyl acetate
  8. customThe layers were separated
  9. extractionThe aqueous layer was extracted with ethyl acetate
  10. washThe combined organic layers were washed with brine
  11. customdried
  12. concentrationconcentrated
  13. customto give a tan oil

出典と根拠

ORDレコード
ord-ec31928b321240b4af0ca23b09fb7515
出典データセット
uspto-grants-2014_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08748429B2

反応ノート

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