Triethylamine → (4S,6S)-4-(2-fluoro-5-((triethylsilyl)ethynyl)phenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine

HRID 930336ノート

反応式

HRID 930336 の反応式
Br[C:2]1[CH:3]=[CH:4][C:5]([F:21])=[C:6]([C@:8]2([CH2:19][F:20])[CH2:13][C@@H:12]([C:14]([F:17])([F:16])[F:15])[O:11][C:10]([NH2:18])=[N:9]2)[CH:7]=1.C(N(CC)CC)C.[CH2:29]([Si:31]([CH2:36][CH3:37])([CH2:34][CH3:35])[C:32]#[CH:33])[CH3:30]>[Cu]I.C1COCC1>[F:21][C:5]1[CH:4]=[CH:3][C:2]([C:30]#[C:29][Si:31]([CH2:36][CH3:37])([CH2:34][CH3:35])[CH2:32][CH3:33])=[CH:7][C:6]=1[C@:8]1([CH2:19][F:20])[CH2:13][C@@H:12]([C:14]([F:17])([F:16])[F:15])[O:11][C:10]([NH2:18])=[N:9]1

参加物

6

反応物 3

HCID 8471TriethylamineHCID 637947(Triethylsilyl)acetyleneHCID 86732143(4S,6S)-4-(5-bromo-2-fluorophenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine

生成物 1

HCID 86732162(4S,6S)-4-(2-fluoro-5-((triethylsilyl)ethynyl)phenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine収率 76%

試薬・触媒・溶媒 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
110 °C

実験手順

A 25 mL microwave vial was charged with (4S,6S)-4-(5-bromo-2-fluorophenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (1.465 g, 3.93 mmol), triethylamine (2.74 mL, 19.63 mmol), 10 mL of THF, triethyl(ethynyl)silane (2.176 mL, 11.78 mmol), Pd(0) tetrakis(triphenylphosphine) (0.343 g, 0.297 mmol), and copper(I) iodide (0.112 g, 0.589 mmol). The resulting mixture was then heated at 110° C. for 30 min in a Biotage microwave synthesizer (waited for 25 min to get on the instrument). The solids were filtered off and the solvent was removed under vacuum and the residue was redissolved in 60 mL of EtOAc, washed with 50 mL of saturated NH4Cl solution twice, dried (Na2SO4) and concentrated to give an oil that was purified by Shoko silica gel instrument (pre-packed GRACE column 120 g, with EtOAc in hexane as eluent, 0-10% 17 min; 10% 8 min; 10-30% 5 min; 30% 10 min) to give the titled compound as a light yellow oil, 1.285 g, 76% yield. MS m/z=433.0 [M+H]+. Calculated for C20H25F5N2OSi: 432.2.

後処理

  1. customto get on the instrument)
  2. filtrationThe solids were filtered off
  3. customthe solvent was removed under vacuum
  4. dissolutionthe residue was redissolved in 60 mL of EtOAc
  5. washwashed with 50 mL of saturated NH4Cl solution twice
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customto give an oil that
  9. customwas purified by Shoko silica gel instrument (pre-packed GRACE column 120 g, with EtOAc in hexane as eluent, 0-10% 17 min; 10% 8 min; 10-30% 5 min; 30% 10 min)

出典と根拠

ORDレコード
ord-579e05ef275448a9b31d7df7921d2889
出典データセット
uspto-grants-2016_03
特許番号
US09296734B2

反応ノート

読み込み中…