Potassium Carbonate → 2-(1', 2'-dihydro-2'-oxospiro[cyclopentane-1,3'-[3H]indol]-5'-yl)-1H pyrrole-1-carboxylic acid, tert-butyl ester

HRID 1609864ノート

反応式

HRID 1609864 の反応式
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]12[CH2:15][CH2:14][CH2:13][CH2:12]1.[C:16]([O:20][C:21]([N:23]1[CH:27]=[CH:26][CH:25]=[C:24]1B(O)O)=[O:22])([CH3:19])([CH3:18])[CH3:17].C(=O)([O-])[O-].[K+].[K+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[O:11]=[C:6]1[C:5]2([CH2:15][CH2:14][CH2:13][CH2:12]2)[C:4]2[C:8](=[CH:9][CH:10]=[C:2]([C:24]3[N:23]([C:21]([O:20][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:22])[CH:27]=[CH:26][CH:25]=3)[CH:3]=2)[NH:7]1

参加物

7

反応物 3

HCID 11430Potassium CarbonateHCID 27343211-(tert-Butoxycarbonyl)-2-pyrroleboronic AcidHCID 120449735'-Bromo-1',2'-dihydrospiro[cyclopentane-1,3'-indole]-2'-one

生成物 1

HCID 120449742-(1', 2'-dihydro-2'-oxospiro[cyclopentane-1,3'-[3H]indol]-5'-yl)-1H pyrrole-1-carboxylic acid, tert-butyl ester収率 83.2%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒2 回HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
80 °C

実験手順

A solution of 5′-bromospiro[cyclopentane-1,3′-[3H]indol]-2′(1′H)-one (2.0 g, 7.5 mmol) and tetrakis(triphenylphosphine)palladium(0) (430 mg, 0.3 mmol) in ethylene glycol dimethyl ether (50 mL) was stirred under a flow of nitrogen for 15 min. To the solution was added sequentially 1-t-butoxycarbonylpyrrole-2-boronic acid (2.1 g, 9.7 mmol) and potassium carbonate (2.4 g, 17 mmol) in water (10 mL). The mixture was heated to 80° C. for 3 h and allowed to cool. The reaction mixture was poured into water (50 mL) and extracted with ethyl acetate (3×50 mL). The organic layers were combined, washed with brine (30 mL) and dried over magnesium sulfate. The solution was filtered and concentrated in vacuo. Crystallization from 20% ethyl acetate/hexane gave 2-(1′,2′-dihydro-2′-oxospiro[cyclopentane-1,3′-[3H]indol]-5′-yl)-1H-pyrrole-1-carboxylic acid, tert-butyl ester (2.2 g, 83%) as a white powder, mp 179–180.5° C. 1H NMR (DMSO-d6, 400 MHz) δ 1.30 (s, 9H), 1.75–1.98 (m, 8H), 6.16 (dd, 1H, J=1.8, 3.3 Hz), 6.22 (‘t’, 1H, J=3.3, 3.3 Hz), 6.79 (d, 1H, J=7.9 Hz), 7.08 (dd, 1H, J=1.8, 7.9 Hz), 7.14 (‘d’, 1H, J=1.5 Hz), 7.28 (dd, J=1.9, 3.3 Hz), 10.30 (s, 1H). MS (EI) m/z 352 [M+]. Anal. Calcd for C21H24N2O3: C, 71.57; H, 6.86; N, 7.95. Found: C, 71.08; H, 6.83; N, 7.74.

後処理

  1. temperatureto cool
  2. extractionextracted with ethyl acetate (3×50 mL)
  3. washwashed with brine (30 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationThe solution was filtered
  6. concentrationconcentrated in vacuo
  7. customCrystallization from 20% ethyl acetate/hexane

出典と根拠

ORDレコード
ord-2e1be7ff63194a95b49803c0b452921b
出典データセット
uspto-grants-2006_01
特許番号
US06982261B2

反応ノート

読み込み中…