3,4-dihydro-2H-pyran → Methyl 2-(1-(3-(tetrahydro-2H-pyran-2-yloxy)phenyl)-2-oxabicyclo[2.2.2]octan-4-yl)acetate

HRID 1855044Notes

Reaction equation

HRID 1855044 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([C:8]23[CH2:15][CH2:14][C:11]([CH2:16][C:17]([O:19][CH3:20])=[O:18])([CH2:12][CH2:13]2)[CH2:10][O:9]3)[CH:5]=[CH:6][CH:7]=1.[O:21]1[CH:26]=[CH:25][CH2:24][CH2:23][CH2:22]1.CC1C=CC(S([O-])(=O)=O)=CC=1.C1C=C[NH+]=CC=1>C(Cl)Cl>[O:21]1[CH2:26][CH2:25][CH2:24][CH2:23][CH:22]1[O:1][C:2]1[CH:3]=[C:4]([C:8]23[CH2:13][CH2:12][C:11]([CH2:16][C:17]([O:19][CH3:20])=[O:18])([CH2:14][CH2:15]2)[CH2:10][O:9]3)[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 80803,4-dihydro-2H-pyranHCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 90408166Methyl 2-(1-(3-hydroxyphenyl)-2-oxabicyclo[2.2.2]octan-4-yl)acetate

Product 1

HCID 90410015Methyl 2-(1-(3-(tetrahydro-2H-pyran-2-yloxy)phenyl)-2-oxabicyclo[2.2.2]octan-4-yl)acetateYield 77%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of methyl 2-(1-(3-hydroxyphenyl)-2-oxabicyclo[2.2.2]octan-4-yl)acetate (887 mg, 3.21 mmol), 3,4-dihydro-2H-pyran (0.5 ml, 5.47 mmol), and PPTS (81 mg, 0.321 mmol) in DCM (10 ml) was stirred at rt for 4 days. The reaction was concentrated in vacuo. The crude oil was purified by flash chromatography on SiO2 (0 to 30% EtOAc:hexanes) to afford the title compound (887 mg, 77% yield) as a white solid. LCMS, [M+NH4]+=378.4. 1H NMR (500 MHz, CDCl3) δ 7.21 (t, J=8.0 Hz, 1H), 7.13-7.08 (m, 1H), 6.99 (ddd, J=7.8, 1.5, 1.0 Hz, 1H), 6.93 (ddd, J=8.2, 2.5, 0.9 Hz, 1H), 5.43 (t, J=3.2 Hz, 1H), 3.97-3.86 (m, 3H), 3.67 (s, 3H), 3.64-3.54 (m, 1H), 2.17 (s, 2H), 2.11-1.96 (m, 5H), 1.90-1.74 (m, 6H), 1.72-1.49 (m, 3H).

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. customThe crude oil was purified by flash chromatography on SiO2 (0 to 30% EtOAc:hexanes)

Sources & evidence

ORD record
ord-386772fd18a14957acaed9c32a2c7c9c
Source dataset
uspto-grants-2015_02
Patent number
US08962660B2

Reaction notes

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