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Tetrahydrofuran → 1-(3,4,5-trimethoxybenzoyl)-3-(2-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-(phenylmethyl)pyrrolidine

HRID 323273
ノート
印刷プレビュー

反応式

HRID 323273 の反応式
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:38]=[C:39]([O:43][CH3:44])[C:40]=1[O:41][CH3:42])[C:6]([N:8]1[CH2:12][CH2:11][C:10]([CH2:20][CH2:21][N:22]2[CH2:27][CH2:26][CH:25]([NH:28][C:29]3[NH:33][C:32]4[CH:34]=[CH:35][CH:36]=[CH:37][C:31]=4[N:30]=3)[CH2:24][CH2:23]2)([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:9]1)=[O:7].[O:45]1[CH2:49][CH2:48][CH2:47][CH2:46]1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].C(OCCCl)C>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C(N(CC)CC)C.O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:38]=[C:39]([O:43][CH3:44])[C:40]=1[O:41][CH3:42])[C:6]([N:8]1[CH2:12][CH2:11][C:10]([CH2:20][CH2:21][N:22]2[CH2:27][CH2:26][CH:25]([NH:28][C:29]3[N:30]([CH2:47][CH2:46][O:45][CH2:49][CH3:48])[C:31]4[CH:37]=[CH:36][CH:35]=[CH:34][C:32]=4[N:33]=3)[CH2:24][CH2:23]2)([CH2:13][C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:9]1)=[O:7]
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

8

反応物 4

HCID 8028TetrahydrofuranHCID 12341Ethane, 1-chloro-2-ethoxy-2 回HCID 3251421Potassium bis(trimethylsilyl)amide2 回HCID 99602911-(3,4,5-trimethoxybenzoyl)-3-(2-(4-(1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-(phenylmethyl)pyrrolidine

生成物 1

HCID 9831217
1-(3,4,5-trimethoxybenzoyl)-3-(2-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-(phenylmethyl)pyrrolidine

試薬・触媒・溶媒 3

HCID 74236Tetrabutylammonium Bromide触媒HCID 962Water溶媒HCID 8471Triethylamine溶媒

反応条件

温度
-78 °C

実験手順

Combine 1-(3,4,5-trimethoxybenzoyl)-3-(2-(4-(1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-(phenylmethyl)pyrrolidine (0.56 g, 0.77 mmol) and tetrahydrofuran (10 mL). Cool to −78° C. using a dry-ice/acetone bath. Add a solution of potassium bis(trimethylsilyl)amide (1.7 mL, 0.5 M in toluene, 0.85 mmol). After 30 minutes, warm to ambient temperature. Add tetrabutylammonium bromide (0.06 g) and 2-chloroethyl ethyl ether (0.092 g 0.85 mmol). Heat to reflux. After 12 hours, potassium bis(trimethylsilyl)amide (0.5 mL, 0.5 M in toluene) and 2-chloroethyl ethyl ether (0.5 mL) and continue to reflux. After 12 hours, cool the reaction and add water. Separate the layers and extract the aqueous layer three times with ethyl acetate. Dry the combined organic layers over Na2SO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting with 2% triethylamine/5% methanol/ethyl acetate to give the title compound: Rf=0.32 (silica gel, 2% triethylamine/5% methanol/ethyl acetate).

後処理

  1. temperaturewarm to ambient temperature
  2. temperatureHeat to reflux
  3. waitAfter 12 hours
  4. temperatureto reflux
  5. waitAfter 12 hours
  6. temperaturecool
  7. customthe reaction
  8. customSeparate the layers
  9. extractionextract the aqueous layer three times with ethyl acetate
  10. dry with materialDry the combined organic layers over Na2SO4
  11. filtrationfilter
  12. customevaporate in vacuo
  13. customto give a residue

出典と根拠

ORDレコード
ord-c8823596a44a4c9fbcc6f6d4df2647a2
出典データセット
uspto-grants-2001_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US06211199B1

反応ノート

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