Pyridine → Methyl 2-(2-(1-(3-(3-(tert-butyldimethylsilyloxy)phenoxy)phenyl)-2-oxabicyclo [2.2.2]octan-4-yl)ethyl)cyclopropanecarboxylate

HRID 1855092ノート

反応式

HRID 1855092 の反応式
[OH:1][C:2]1[CH:3]=[C:4]([C:8]23[CH2:15][CH2:14][C:11]([CH2:16][CH2:17][CH:18]4[CH2:20][CH:19]4[C:21]([O:23][CH3:24])=[O:22])([CH2:12][CH2:13]2)[CH2:10][O:9]3)[CH:5]=[CH:6][CH:7]=1.[Si:25]([O:32][C:33]1[CH:34]=[C:35](B(O)O)[CH:36]=[CH:37][CH:38]=1)([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26].N1C=CC=CC=1.CC1C=CC(S(OCC23CCC(C4SC(C)=NC=4C4C=CC=CC=4)(CC2)OC3)(=O)=O)=CC=1>C(Cl)Cl.CC([O-])=O.CC([O-])=O.[Cu+2]>[Si:25]([O:32][C:33]1[CH:34]=[C:35]([CH:36]=[CH:37][CH:38]=1)[O:1][C:2]1[CH:3]=[C:4]([C:8]23[CH2:15][CH2:14][C:11]([CH2:16][CH2:17][CH:18]4[CH2:20][CH:19]4[C:21]([O:23][CH3:24])=[O:22])([CH2:12][CH2:13]2)[CH2:10][O:9]3)[CH:5]=[CH:6][CH:7]=1)([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26]

参加物

7

反応物 4

HCID 1049PyridineHCID 34630293-(tert-Butyldimethylsilyloxy)phenylboronic AcidHCID 90408261Methyl 2-(2-(1-(3-hydroxyphenyl)-2-oxabicyclo[2.2.2]octan-4-yl)ethyl)cyclopropane-carboxylateHCID 90408478(1-(2-Methyl-4-phenylthiazol-5-yl)-2-oxabicyclo[2.2.2]octan-4-yl)methyl 4-methylbenzenesulfonate

生成物 1

HCID 90409051Methyl 2-(2-(1-(3-(3-(tert-butyldimethylsilyloxy)phenoxy)phenyl)-2-oxabicyclo [2.2.2]octan-4-yl)ethyl)cyclopropanecarboxylate収率 97.2%

試薬・触媒・溶媒 2

HCID 8895Cupric acetate触媒HCID 6344Dichloromethane溶媒

実験手順

A mixture of methyl 2-(2-(1-(3-hydroxyphenyl)-2-oxabicyclo[2.2.2]octan-4-yl)ethyl)cyclopropane-carboxylate (65B; 360 mg, 1.09 mmol), (3-((tert-butyldimethylsilyl)oxy)phenyl)boronic acid (340 mg, 1.348 mmol), Cu(OAc)2 (237 mg, 1.31 mmol), TEA (1.52 mL, 10.9 mmol), pyridine (0.88 mL, 10.9 mmol), and 4A molecular sieves (5 g) in DCM (10 mL) was stirred under air at rt for 3 days. The reaction was then filtered, and the filtrate was concentrated in vacuo. The residual crude oil was dissolved in EtOAc (15 mL) and washed with 1N aq. HCl and water, dried (MgSO4), and filtered. The filtrate was concentrated in vacuo. The residual crude oil was chromatographed (SiO2; gradient from 0% to 30% over 10 min EtOAc/hexane) to give the title compound (570 mg, 1.06 mmol, 97% yield) as a clear oil. LCMS [M+H]+=537.3; 1H NMR (CDCl3) δ: 7.26 (t, J=7.9 Hz, 1H), 7.18-7.11 (m, 2H), 7.09 (dd, J=2.5, 1.7 Hz, 1H), 6.85 (ddd, J=8.1, 2.5, 1.0 Hz, 1H), 6.58 (dd, J=8.2, 2.3 Hz, 2H), 6.49 (t, J=2.3 Hz, 1H), 3.78 (d, J=1.1 Hz, 2H), 3.68 (s, 3H), 2.00 (dt, J=11.4, 4.1 Hz, 4H), 1.62 (dtd, J=8.1, 4.1, 3.5, 2.0 Hz, 4H), 1.41-1.14 (m, 7H), 0.97 (s, 9H), 0.71 (ddd, J=8.1, 6.3, 4.1 Hz, 1H), 0.18 (s, 6H).

後処理

  1. filtrationThe reaction was then filtered
  2. concentrationthe filtrate was concentrated in vacuo
  3. dissolutionThe residual crude oil was dissolved in EtOAc (15 mL)
  4. washwashed with 1N aq. HCl and water
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo
  8. customThe residual crude oil was chromatographed (SiO2; gradient from 0% to 30% over 10 min EtOAc/hexane)

出典と根拠

ORDレコード
ord-6299f02186304225bb74d4abfc465d63
出典データセット
uspto-grants-2015_02
特許番号
US08962660B2

反応ノート

読み込み中…