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 2285361노트

반응식

HRID 2285361 반응식
[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]

참가 물질

7

반응물 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

생성물 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 acid수율 31%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 312751,4-Dioxane용매

반응 조건

온도
100 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-b28085bcb4814c6cb7fc5d551077639e
출처 데이터셋
uspto-grants-2015_09
특허 번호
US09145441B2

반응 노트

불러오는 중…