Cyclohexane, (bromomethyl)- → 2-(2-(1-(3-(Cyclohexylmethoxy)phenyl)-2-oxabicyclo[2.2.2]octan-4-yl)ethoxy)acetic acid

HRID 1855081Notes

Reaction equation

HRID 1855081 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([C:8]23[CH2:15][CH2:14][C:11]([CH2:16][CH2:17][O:18][CH2:19][C:20]([O:22]C(C)(C)C)=[O:21])([CH2:12][CH2:13]2)[CH2:10][O:9]3)[CH:5]=[CH:6][CH:7]=1.Br[CH2:28][CH:29]1[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1>>[CH:29]1([CH2:28][O:1][C:2]2[CH:3]=[C:4]([C:8]34[CH2:15][CH2:14][C:11]([CH2:16][CH2:17][O:18][CH2:19][C:20]([OH:22])=[O:21])([CH2:12][CH2:13]3)[CH2:10][O:9]4)[CH:5]=[CH:6][CH:7]=2)[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1

Participants

3

Reactant 2

HCID 137636Cyclohexane, (bromomethyl)-HCID 90408312tert-Butyl 2-(2-(1-(3-hydroxyphenyl)-2-oxabicyclo[2.2.2]octan-4-yl)ethoxy)acetate

Product 1

HCID 904091222-(2-(1-(3-(Cyclohexylmethoxy)phenyl)-2-oxabicyclo[2.2.2]octan-4-yl)ethoxy)acetic acidYield 65%

Procedure

The title compound was prepared by an analogous sequence to that used to synthesize Example 51 from 7F (tert-butyl 2-(2-(1-(3-hydroxyphenyl)-2-oxabicyclo[2.2.2]octan-4-yl)ethoxy)acetate) except that (bromomethyl)cyclohexane was used instead of (bromomethyl)cyclobutane as the alkylating agent. The crude product was purified by preparative LC/MS (Column: Waters XBridge C18, 19×200 mm, 5-nm particles; Mobile Phase A: 5:95 MeCN:water with 10-mM NH4OAc; Mobile Phase B: 95:5 MeCN:water with 10-mM NH4OAc; Gradient: 30-70% B over 20 min, then a 5-min hold at 100% B; Flow rate: 20 mL/min) to give the title compound (8 mg, 65% yield; 100% purity by LC/MS) as a light yellow oil. LCMS, [M−H]−=401. 1H NMR (500 MHz, DMSO-d6) δ 7.96 (s, 1H), 7.17 (t, J=8.1 Hz, 1H), 6.96-6.85 (m, 2H), 6.78-6.68 (m, 1H), 3.95 (s, 2H), 3.79-3.70 (m, 4H), 3.50 (t, J=6.7 Hz, 3H), 2.08-1.98 (m, 2H), 1.86-1.57 (m, 12H), 1.40 (t, J=6.7 Hz, 2H), 1.32-1.12 (m, 3H), 1.10-0.99 (m, 2H).

Workup

  1. customThe title compound was prepared by an analogous sequence to
  2. customThe crude product was purified by preparative LC/MS (Column
  3. customa 5-min hold

Sources & evidence

ORD record
ord-2bb4fd63d9394f09a37b8d7fbc664708
Source dataset
uspto-grants-2015_02
Patent number
US08962660B2

Reaction notes

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