3-Chloro-5-fluorobenzo[b]thiophene-2-carbonyl chloride → (3-Chloro-7-fluoro-benzo[b]thiophen-2-yl)methanol

HRID 2097050ノート

反応式

HRID 2097050 の反応式
ClC1C2C=C(F)C=CC=2SC=1C(Cl)=O.[Cl:15][C:16]1[C:17]2[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[C:18]=2[S:19][C:20]=1[C:21](Cl)=[O:22].[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[Cl:15][C:16]1[C:17]2[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[C:18]=2[S:19][C:20]=1[CH2:21][OH:22]

参加物

5

反応物 3

HCID 148724863-Chloro-5-fluorobenzo[b]thiophene-2-carbonyl chlorideHCID 21226445Aluminium lithium hydrideHCID 592776183-Chloro-7-fluoro-benzo[b]thiophene-2-carbonyl chloride

生成物 1

HCID 59277539(3-Chloro-7-fluoro-benzo[b]thiophen-2-yl)methanol収率 11.7%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

To an ice-cold suspension of a 6:1 mixture of 3-chloro-5-fluoro-benzo[b]thiophene-2-carbonyl chloride and 3-chloro-7-fluoro-benzo[b]thiophene-2-carbonyl chloride (5.46 g, 23.6 mmol) in THF (120 mL) was added lithium aluminum hydride (11.8 mL of a 1.0 M solution in THF, 11.8 mmol) dropwise. The mixture was stirred for 4 h then quenched with NaOH (0.35 N solution in H2O). The mixture was diluted with Et2O and the solution filtered. The filtrate was dried (Na2SO4) and concentrated. Purification by flash column chromatography (silica gel, hexanes/EtOAc, 9:1 to hexanes/EtOAc 8:2) gave the title compound (600 mg, 4% (2 steps), 7-fluoro isomer) as a light, yellow solid: 1H NMR (300 MHz, CDCl3) δ 7.59 (d, J=8.0 Hz, 1H), 7.41 (ddd, J=8.0, 8.0, 4.9 Hz, 1H), 7.10 (dd, J=9.1, 9.1 Hz, 1H), 5.00 (d, J=6.2 Hz, 2H), 2.04 (t, J=6.5 Hz, 1H).

後処理

  1. customthen quenched with NaOH (0.35 N solution in H2O)
  2. additionThe mixture was diluted with Et2O
  3. filtrationthe solution filtered
  4. dry with materialThe filtrate was dried (Na2SO4)
  5. concentrationconcentrated
  6. customPurification by flash column chromatography (silica gel, hexanes/EtOAc, 9:1 to hexanes/EtOAc 8:2)

出典と根拠

ORDレコード
ord-9639bfca526f44d385098acf98e10663
出典データセット
uspto-grants-2013_05
特許番号
US08450307B2

反応ノート

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