Hydrochloric Acid → (3R)-4,4,4-Trifluoro-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butanal

HRID 1843598ノート

反応式

HRID 1843598 の反応式
[F:1][C:2]([F:30])([F:29])[C@H:3]([N:7]1[CH:11]=[C:10]([C:12]2[C:13]3[CH:20]=[CH:19][N:18]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:14]=3[N:15]=[CH:16][N:17]=2)[CH:9]=[N:8]1)[CH2:4][C:5]#N.[H-].C([Al+]CC(C)C)C(C)C.C[OH:42].Cl>C(Cl)Cl.O>[F:1][C:2]([F:29])([F:30])[C@H:3]([N:7]1[CH:11]=[C:10]([C:12]2[C:13]3[CH:20]=[CH:19][N:18]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:26])([CH3:27])[CH3:28])[C:14]=3[N:15]=[CH:16][N:17]=2)[CH:9]=[N:8]1)[CH2:4][CH:5]=[O:42]

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 21225700DiisobutylaluminumhydrideHCID 57478054(3R)-4,4,4-trifluoro-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butanenitrile

生成物 1

HCID 59159509(3R)-4,4,4-Trifluoro-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butanal収率 84.3%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6344Dichloromethane溶媒2 回

反応条件

温度
-47.5 °C

実験手順

To a −70° C. solution of (3R)-4,4,4-trifluoro-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butanenitrile (1.06 g, 0.00243 mol) (see, Example 93, Step 1) in DCM (10 mL, 0.2 mol) was added 1.0 M diisobutylaluminum hydride in DCM (4.8 mL). The resulting mixture was stirred for 3 h and allowed to warm during this time interval from −70 to −25° C., after which the reaction was cooled back at −70° C. Methanol (1.5 mL, 0.037 mol) was added, followed by 2.0 M HCl in water (15 mL). Insoluble material was then filtered from the reaction mixture. The organic filtrate was washed sequentially with: 2.0 M HCl in water, water and saturated aqueous NaCl. The washed organic phase was dried over sodium sulfate and was concentrated using a rotory evaporator to give 0.58 g of the crude product as a pale yellow foam/solid. The crude product was chromatographed with 0-80% ethyl acetate/hexanes to give the purified product (0.9 g) as a pale orange oil (47% yield).

後処理

  1. temperatureafter which the reaction was cooled back at −70° C
  2. filtrationInsoluble material was then filtered from the reaction mixture
  3. washThe organic filtrate was washed sequentially with: 2.0 M HCl in water, water and saturated aqueous NaCl
  4. dry with materialThe washed organic phase was dried over sodium sulfate
  5. concentrationwas concentrated
  6. customa rotory evaporator
  7. customto give 0.58 g of the crude product as a pale yellow foam/solid
  8. customThe crude product was chromatographed with 0-80% ethyl acetate/hexanes

出典と根拠

ORDレコード
ord-ab3d4e09b6f9406c8bf9e869ff60b8f7
出典データセット
uspto-grants-2015_02
特許番号
US08946245B2

反応ノート

読み込み中…