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Isopropyl chloroformate → 1-Methylethyl 4-({[2'-fluoro-4'-(methylsulfonyl)-4-biphenylyl]oxy}methyl)-1-piperidinecarboxylate

HRID 423500
ノート
印刷プレビュー

反応式

HRID 423500 の反応式
C(N(C(C)C)CC)(C)C.Cl.[F:11][C:12]1[CH:17]=[C:16]([S:18]([CH3:21])(=[O:20])=[O:19])[CH:15]=[CH:14][C:13]=1[C:22]1[CH:27]=[CH:26][C:25]([O:28][CH2:29][CH:30]2[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]2)=[CH:24][CH:23]=1.Cl[C:37]([O:39][CH:40]([CH3:42])[CH3:41])=[O:38]>C(Cl)Cl>[F:11][C:12]1[CH:17]=[C:16]([S:18]([CH3:21])(=[O:20])=[O:19])[CH:15]=[CH:14][C:13]=1[C:22]1[CH:23]=[CH:24][C:25]([O:28][CH2:29][CH:30]2[CH2:35][CH2:34][N:33]([C:37]([O:39][CH:40]([CH3:42])[CH3:41])=[O:38])[CH2:32][CH2:31]2)=[CH:26][CH:27]=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

5

反応物 3

HCID 7917Isopropyl chloroformateHCID 81531DiisopropylethylamineHCID 666734284-({[2'-Fluoro-4'-(methylsulfonyl)-4-biphenylyl]oxy}methyl)piperidine hydrochloride

生成物 1

HCID 249940291-Methylethyl 4-({[2'-fluoro-4'-(methylsulfonyl)-4-biphenylyl]oxy}methyl)-1-piperidinecarboxylate収率 98%

試薬・触媒・溶媒 1

HCID 6344
Dichloromethane
溶媒

反応条件

温度
0 °C

実験手順

Diisopropylethylamine (0.14 mL, 0.75 mmol) was added to a suspension of 4-({[2′-fluoro-4′-(methylsulfonyl)-4-biphenylyl]oxy}methyl)piperidine hydrochloride (0.10 g, 0.25 mmol) in CH2Cl2 (7 mL). The mixture was cooled to 0° C. in an ice bath, and isopropyl chloroformate (1.0M in toluene, 0.28 mL, 0.28 mmol) was added dropwise. The reaction mixture was allowed to warm to ambient temperature, and stirred overnight. The mixture was then concentrated to give the crude product as a colorless oil. The crude product was purified by chromatography on a silica gel column eluted with 5:6 EtOAc/hexane to give 0.11 g (98%) of the title compound as a white solid. 1H NMR (400 MHz, CDCl3): δ 7.80-7.70 (m, 2H), 7.65-7.55 (m, 1H), 7.50 (d, 2H, J=8.8 Hz), 6.98 (d, 2H, J=8.6 Hz), 4.92 (septet, 1H, J=6.1 Hz), 4.25-4.15 (m, 2H), 3.86 (d, 2H, J=6.3 Hz), 3.09 (s, 3H), 2.85-2.75 (m, 2H), 2.10-1.90 (m, 1H), 1.90-1.80 (m, 2H), 1.35-1.10 (m, 8H); LRMS (ESI), m/z 450 (M+H).

後処理

  1. temperatureto warm to ambient temperature
  2. concentrationThe mixture was then concentrated
  3. customto give the crude product as a colorless oil
  4. customThe crude product was purified by chromatography on a silica gel column
  5. washeluted with 5:6 EtOAc/hexane

出典と根拠

ORDレコード
ord-2ce4be78b7bb4eefbbff4ccde71f3a03
出典データセット
uspto-grants-2012_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08101634B2

反応ノート

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