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Cesium carbonate → (+/-) Tert-butyl (3-(3-(((tert-butyldimethylsilyl)oxy)methyl)-4-(oxetan-3-yl)piperazin-1-yl)-2-chloro-5-cyanophenyl)carbamate

HRID 1430867
ノート
印刷プレビュー

反応式

HRID 1430867 の反応式
Br[C:2]1[C:3]([Cl:18])=[C:4]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH:5]=[C:6]([C:8]#[N:9])[CH:7]=1.[Si:19]([O:26][CH2:27][CH:28]1[CH2:33][NH:32][CH2:31][CH2:30][N:29]1[CH:34]1[CH2:37][O:36][CH2:35]1)([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[Si:19]([O:26][CH2:27][CH:28]1[N:29]([CH:34]2[CH2:37][O:36][CH2:35]2)[CH2:30][CH2:31][N:32]([C:2]2[C:3]([Cl:18])=[C:4]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH:5]=[C:6]([C:8]#[N:9])[CH:7]=2)[CH2:33]1)([C:22]([CH3:25])([CH3:23])[CH3:24])([CH3:21])[CH3:20]
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

7

反応物 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 86708481Tert-butyl (3-bromo-2-chloro-5-cyanophenyl)carbamateHCID 867085572-(((Tert-butyldimethylsilyl)oxy)methyl)-1-(oxetan-3-yl)piperazine

生成物 1

HCID 86708559(+/-) Tert-butyl (3-(3-(((tert-butyldimethylsilyl)oxy)methyl)-4-(oxetan-3-yl)piperazin-1-yl)-2-chloro-5-cyanophenyl)carbamate
収率 62.4%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 1140Toluene溶媒

反応条件

温度
105 °C

実験手順

(+/−) Tert-butyl (3-bromo-2-chloro-5-cyanophenyl)carbamate (545 mg, 1.644 mmol), 2-(((tert-butyldimethylsilyl)oxy)methyl)-1-(oxetan-3-yl)piperazine (518 mg, 1.808 mmol), Pd2(dba)3 (151 mg, 0.164 mmol), BINAP (102 mg, 0.164 mmol), Cs2CO3 (1071 mg, 3.29 mmol), and Toluene (16 mL) were combined in a 2 dram vial. The vial was evacuated and backfilled with Ar 3×, and the reaction was heated at 105° C. for 18 h. The reaction was cooled to rt and diluted with MeOH. The solution was filtered through celite and the filtrate concentrated in vacuo. The crude material was purified by flash column chromatography (0-50% EtOAc/Hex). (+/−) tert-butyl (3-(3-(((tert-butyldimethylsilyl)oxy)methyl)-4-(oxetan-3-yl)piperazin-1-yl)-2-chloro-5-cyanophenyl)carbamate (551 mg) was obtained as an orange glass.

後処理

  1. customThe vial was evacuated
  2. temperatureThe reaction was cooled to rt
  3. additiondiluted with MeOH
  4. filtrationThe solution was filtered through celite
  5. concentrationthe filtrate concentrated in vacuo
  6. customThe crude material was purified by flash column chromatography (0-50% EtOAc/Hex)

出典と根拠

ORDレコード
ord-e259b33b1a7049e5b4aa8171ccc87f17
出典データセット
uspto-grants-2015_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08940736B2

反応ノート

読み込み中…

このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート