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

HRID 2285361ノート

反応式

HRID 2285361 の反応式
[C:1]([Si:5]([CH3:16])([CH3:15])[O:6][C@@H:7]([C@@H:9]([CH:13]=[CH2:14])[C:10]([OH:12])=[O:11])[CH3:8])([CH3:4])([CH3:3])[CH3:2].Br[C:18]1[CH:27]=[C:26]2[C:21]([CH:22]=[CH:23][C:24]([C@H:28]([O:30][C:31](=[O:33])[CH3:32])[CH3:29])=[N:25]2)=[CH:20][CH:19]=1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C1(CNCC2CCCCC2)CCCCC1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:31]([O:30][C@@H:28]([C:24]1[CH:23]=[CH:22][C:21]2[C:26](=[CH:27][C:18](/[CH:14]=[CH:13]/[C@H:9]([C@H:7]([O:6][Si:5]([C:1]([CH3:4])([CH3:3])[CH3:2])([CH3:16])[CH3:15])[CH3:8])[C:10]([OH:12])=[O:11])=[CH:19][CH:20]=2)[N:25]=1)[CH3:29])(=[O:33])[CH3:32]

参加物

7

反応物 4

HCID 80271Tri-o-tolylphosphineHCID 4594378Bis(cyclohexylmethyl)amineHCID 86709645acetic acid (R)-1-(7-bromo-quinolin-2-yl)-ethyl esterHCID 86709657(R)-2-[(R)-1-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-but-3-enoic acid

生成物 1

HCID 86709658(E)-(R)-4-[2-((R)-1-Acetoxy-ethyl)-quinolin-7-yl]-2-[(R)-1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-but-3-enoic acid収率 31%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

A solution of (R)-2-[(R)-1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-but-3-enoic acid (200 mg, 0.82 mmol), acetic acid (R)-1-(7-bromo-quinolin-2-yl)-ethyl ester (241 mg, 0.82 mmol), palladium(II) acetate (37 mg, 0.16 mmol), tri-(o-tolyl)phosphine (50 mg, 0.16 mmol) in anhydrous 1,4-dioxane (10 mL) was treated with N,N-dicylohexylmethylamine (280 μL, 1.31 mmol). After stirring at 100° C. for 6 h, the reaction was cooled to room temperature, filtered off and the volatiles were removed in vacuo. The residue was partitioned between ethyl acetate and hydrochloric acid (1 M). 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 dichloromethane/methanol 1:0 to 9:1 to afford the title compound (115 mg, 31%) as a colourless oil. 1H NMR (300 MHz, CDCl3) δ 0.10 (s, 3H), 0.11 (s, 3H), 0.89 (s, 9H), 1.25 (d, J=6.0 Hz, 3H), 1.68 (d, J=6.4 Hz, 3H), 2.17 (s, 3H), 3.22-3.37 (m, 1H), 3.65-3.80 (m, 1H), 4.26 (pentet, J=6.7 Hz, 1H), 6.08 (q, J=6.7 Hz, 1H), 6.40 (dd, J=15.8, 9.1 Hz, 1H), 6.76 (d, J=15.8 Hz, 1H), 7.42 (d, J=8.7 Hz, 1H), 7.40-7.55 (m, 1H), 7.55-7.75 (m, 1H), 8.03 (s, 1H), 8.11 (d, J=8.5 Hz, 1H). LCMS (m/z) 458.2 [M+H], Tr=3.45 min.

後処理

  1. temperaturethe reaction was cooled to room temperature
  2. filtrationfiltered off
  3. customthe volatiles were removed in vacuo
  4. customThe residue was partitioned between ethyl acetate and hydrochloric acid (1 M)
  5. customthe volatiles were removed in vacuo
  6. customThe residue was purified by silica gel chromatography
  7. washeluted with a continuous gradient of dichloromethane/methanol 1:0 to 9:1

出典と根拠

ORDレコード
ord-b28085bcb4814c6cb7fc5d551077639e
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…