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

HRID 1855092노트

반응식

HRID 1855092 반응식
[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]

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 8895Cupric acetate촉매HCID 6344Dichloromethane용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-6299f02186304225bb74d4abfc465d63
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08962660B2

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