Triethylamine → (E)-4-[2-((R)-1-Acetoxy-ethyl)-quinolin-7-yl]-2-[1-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-2-methyl-but-3-enoic acid

HRID 2285389ノート

反応式

HRID 2285389 の反応式
[C:1]([Si:5]([CH3:18])([CH3:17])[O:6][C:7]([C:10]([CH3:16])([CH:14]=[CH2:15])[C:11]([OH:13])=[O:12])([CH3:9])[CH3:8])([CH3:4])([CH3:3])[CH3:2].Br[C:20]1[CH:29]=[C:28]2[C:23]([CH:24]=[CH:25][C:26]([C@H:30]([O:32][C:33](=[O:35])[CH3:34])[CH3:31])=[N:27]2)=[CH:22][CH:21]=1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)CC)C>C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:33]([O:32][C@@H:30]([C:26]1[CH:25]=[CH:24][C:23]2[C:28](=[CH:29][C:20](/[CH:15]=[CH:14]/[C:10]([C:7]([O:6][Si:5]([C:1]([CH3:4])([CH3:3])[CH3:2])([CH3:18])[CH3:17])([CH3:8])[CH3:9])([CH3:16])[C:11]([OH:13])=[O:12])=[CH:21][CH:22]=2)[N:27]=1)[CH3:31])(=[O:35])[CH3:34]

参加物

7

反応物 4

HCID 8471TriethylamineHCID 80271Tri-o-tolylphosphineHCID 86709645acetic acid (R)-1-(7-bromo-quinolin-2-yl)-ethyl esterHCID 867096802-[1-(tert-Butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-2-methyl-but-3-enoic acid

生成物 1

HCID 86709681(E)-4-[2-((R)-1-Acetoxy-ethyl)-quinolin-7-yl]-2-[1-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-2-methyl-but-3-enoic acid収率 65%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 6342Acetonitrile溶媒

反応条件

温度
100 °C

実験手順

A solution of 2-[1-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-2-methyl-but-3-enoic acid (258 mg, 0.95 mmol), acetic acid (R)-1-(7-bromo-quinolin-2-yl)-ethyl ester (279 mg, 0.95 mmol), palladium(II) acetate (43 mg, 0.19 mmol), tris-(o-tolyl)phosphine (87 mg, 0.29 mmol) in anhydrous acetonitrile (3 mL) was treated with triethylamine (265 μL, 1.90 mmol). After stirring at 100° C. under microwave for 20 min, the reaction was cooled to room temperature and the volatiles were removed in vacuo. The residue was partitioned between dichloromethane and a saturated potassium hydrogen sulfate solution. The organics were combined and the volatiles were removed in vacuo. The residue was purified by silica gel chromatography using a 25 g Biotage cartridge eluted with a continuous gradient of iso-hexanes/ethyl acetate 1:0 to 0:1 to afford the title compound (300 mg, 65%) as a colourless oil. 1H NMR (300 MHz, CDCl3) δ 0.20 (s, 3H), 0.22 (s, 3H), 0.94 (s, 9H), 1.44 (s, 3H), 1.45 (s, 3H), 1.50 (s, 3H), 1.68 (d, J=6.7 Hz, 3H), 2.17 (s, 3H), 6.06 (q, J=6.7 Hz, 1H), 6.76 (m, 2H), 7.43 (d, J=8.5 Hz, 1H), 7.62 (d, J=8.5 Hz, 1H), 7.74 (d, J=8.7 Hz, 1H), 8.03 (s, 1H), 8.11 (d, J=8.5 Hz, 1H). LCMS (m/z) 486.3 [M+H], Tr=3.64 min.

後処理

  1. temperaturethe reaction was cooled to room temperature
  2. customthe volatiles were removed in vacuo
  3. customThe residue was partitioned between dichloromethane
  4. customthe volatiles were removed in vacuo
  5. customThe residue was purified by silica gel chromatography
  6. washeluted with a continuous gradient of iso-hexanes/ethyl acetate 1:0 to 0:1

出典と根拠

ORDレコード
ord-6a34996246f540a79ef8f71d59ceafe0
出典データセット
uspto-grants-2015_09
特許番号
US09145441B2

反応ノート

読み込み中…