Diethylamine → butyl 4-(4-((S)-1-((S)-6-(2-hydroxy-2-methylpropyl)-2-oxo-6-phenyl-1,3-oxazinan-3-yl)ethyl)phenyl)-2,2-dimethylbut-3-ynoate

HRID 333895ノート

反応式

HRID 333895 の反応式
Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([N:10]2[CH2:15][CH2:14][C@:13]([CH2:22][C:23]([OH:26])([CH3:25])[CH3:24])([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[O:12][C:11]2=[O:27])[CH3:9])=[CH:4][CH:3]=1.[CH3:28][C:29]([CH3:39])([C:37]#[CH:38])[C:30]([O:32][CH2:33][CH2:34][CH2:35][CH3:36])=[O:31].N(CC)CC>[Cu]I.Cl[Pd](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.CCN(CC)CC>[OH:26][C:23]([CH3:25])([CH3:24])[CH2:22][C@@:13]1([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[O:12][C:11](=[O:27])[N:10]([C@H:8]([C:5]2[CH:6]=[CH:7][C:2]([C:38]#[C:37][C:29]([CH3:28])([CH3:39])[C:30]([O:32][CH2:33][CH2:34][CH2:35][CH3:36])=[O:31])=[CH:3][CH:4]=2)[CH3:9])[CH2:15][CH2:14]1

参加物

7

反応物 3

HCID 8021DiethylamineHCID 44599033(S)-3-((S)-1-(4-bromophenyl)ethyl)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-oneHCID 86670540Butyl 2,2-dimethylbut-3-ynoate

生成物 1

HCID 66869601butyl 4-(4-((S)-1-((S)-6-(2-hydroxy-2-methylpropyl)-2-oxo-6-phenyl-1,3-oxazinan-3-yl)ethyl)phenyl)-2,2-dimethylbut-3-ynoate収率 19%

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418476HCID 178418476、化合物触媒HCID 8471Triethylamine溶媒

実験手順

A microwave vial was charged with (S)-3-((S)-1-(4-bromophenyl)ethyl)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one (50 mg, 0.12 mmol), butyl 2,2-dimethylbut-3-ynoate (40 mg, 0.23 mmol), CuI (2.2 mg, 0.012 mmol), PdCl2(PPh3)2 (5 mg, 0.008 mmol), Et3N (2 mL) and Et2NH (0.2 mL). The mixture was sparged with N2 for 10 min and heated at 100 C for 2 h. The mixture was concentrated, redissolved in EtOAc (90 mL), washed with 5% aq HCl (20 mL) and brine (20 mL), and dried over Na2SO4. Removal of the solvent left an oil (75 mg) which was purified by prep HPLC to afford butyl 4-(4-((S)-1-((S)-6-(2-hydroxy-2-methylpropyl)-2-oxo-6-phenyl-1,3-oxazinan-3-yl)ethyl)phenyl)-2,2-dimethylbut-3-ynoate (11 mg, 19%). LC-MS Method 1 tR=2.13 min, m/z=520, 462.

後処理

  1. customThe mixture was sparged with N2 for 10 min
  2. temperatureheated at 100 C for 2 h
  3. concentrationThe mixture was concentrated
  4. dissolutionredissolved in EtOAc (90 mL)
  5. washwashed with 5% aq HCl (20 mL) and brine (20 mL)
  6. dry with materialdried over Na2SO4
  7. customRemoval of the solvent
  8. waitleft an oil (75 mg) which
  9. customwas purified by prep HPLC

出典と根拠

ORDレコード
ord-6cef5154ed044f349946c02c07e55479
出典データセット
uspto-grants-2014_11
特許番号
US08883778B2

反応ノート

読み込み中…