2-Methyl-3-butyn-2-ol → (S)-tert-butyl 1-(N-(4-(3-hydroxy-3-methylbut-1-ynyl)thiazol-2-yl)-tert-butoxylcarbonylamino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate

HRID 2109727ノート

反応式

HRID 2109727 の反応式
Br[C:2]1[N:3]=[C:4]([N:7]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:8][C@@H:9]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)[S:5][CH:6]=1.[CH3:36][C:37]([OH:41])([C:39]#[CH:40])[CH3:38]>CCN(CC)CC.Cl[Pd-2](Cl)(P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[OH:41][C:37]([CH3:38])([CH3:36])[C:39]#[C:40][C:2]1[N:3]=[C:4]([N:7]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:8][C@@H:9]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)[S:5][CH:6]=1

参加物

6

反応物 2

HCID 82582-Methyl-3-butyn-2-olHCID 57633952(S)-tert-butyl 1-(N-(4-bromothiazol-2-yl)-tert-butoxylcarbonylamino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate

生成物 1

HCID 57634169(S)-tert-butyl 1-(N-(4-(3-hydroxy-3-methylbut-1-ynyl)thiazol-2-yl)-tert-butoxylcarbonylamino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate収率 91.6%

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418903HCID 178418903、化合物触媒HCID 8471Triethylamine溶媒

反応条件

温度
60 °C

実験手順

(S)-tert-butyl 1-(N-(4-bromothiazol-2-yl)-tert-butoxylcarbonylamino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate (0.25 g, 0.43 mmol) was taken up in 4 mL of Et3N. 2-Methylbut-3-yn-2-ol (0.21 mL, 2.2 mmol), dichlorobis(triphenylphosphino)-palladium(II) (0.030 g, 0.043 mmol), and copper(I) iodide (0.025 g, 0.13 mmol) were added. The mixture was stirred for 20 minutes. No reaction was observed, and the mixture was heated to 60° C. for 1 hour. The reaction was judged to be complete by LC/MS, the solvent was removed under reduced pressure, and the residue was purified by flash chromatography on silica gel (5% to 30% EtOAc/hexanes), to provide (S)-tert-butyl 1-(N-(4-(3-hydroxy-3-methylbut-1-ynyl)thiazol-2-yl)-tert-butoxylcarbonylamino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate (0.23 g, 91% yield): LCMS (M+H) 584 calc. for C28H37F3N3O5S 583.6.

後処理

  1. customthe solvent was removed under reduced pressure
  2. customthe residue was purified by flash chromatography on silica gel (5% to 30% EtOAc/hexanes)

出典と根拠

ORDレコード
ord-334c54762a7344baae5415e354e78054
出典データセット
uspto-grants-2009_04
特許番号
US07514566B2

反応ノート

読み込み中…