Sodium Hydroxide → HCID 90408389, compound

HRID 1855072Notes

Reaction equation

HRID 1855072 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:15]23[CH2:22][CH2:21][C:18]([CH2:23][CH2:24][OH:25])([CH2:19][CH2:20]2)[CH2:17][O:16]3)[CH:5]=[C:6]([O:8][CH:9]2[CH2:14][CH2:13][CH2:12][CH2:11][O:10]2)[CH:7]=1.[OH-].[Na+].Br[CH2:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31]>C1(C)C=CC=CC=1.[N+](CCCC)(CCCC)(CCCC)CCCC.[Cl-].O>[F:1][C:2]1[CH:3]=[C:4]([C:15]23[CH2:20][CH2:19][C:18]([CH2:23][CH2:24][O:25][CH2:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])([CH2:21][CH2:22]2)[CH2:17][O:16]3)[CH:5]=[C:6]([O:8][CH:9]2[CH2:14][CH2:13][CH2:12][CH2:11][O:10]2)[CH:7]=1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 79177tert-Butyl bromoacetateHCID 90408708HCID 90408708, compound

Product 1

HCID 90408389HCID 90408389, compoundYield 86.1%

Reagents, catalysts & solvents 2

HCID 16212273Tetrabutylammonium chloride hydrateCatalystHCID 1140TolueneSolvent

Procedure

To a solution of 2-(1-(3-fluoro-5-(tetrahydro-2H-pyran-2-yloxy)phenyl)-2-oxabicyclo[2.2.2]octan-4-yl) ethanol (350 mg, 1.00 mmol) in toluene (1 mL) was added Bu4NCl.H2O (89 mg, 0.300 mmol). The reaction mixture was cooled to 0° C. after which aqueous 35% NaOH (10 mL) and tert-butyl bromoacetate (295 μL, 1.99 mmol) were successively added. The reaction was stirred at rt for 18 h. The organic layer was separated, washed with H2O (5×15 mL) and brine (15 mL) until the pH=7, and then was concentrated in vacuo. The residual crude oil was purified by flash chromatography (SiO2) using a gradient from 0% to 30% EtOAc/hexane (10 min) to give the title compound (400 mg, 0.861 mmol, 86% yield) as a clear oil. 1H NMR (500 MHz, CDCl3) δ: 6.86 (t, J=1.7 Hz, 1H), 6.77-6.72 (m, 1H), 6.67 (d, J=10.5 Hz, 1H), 5.39 (s, 1H), 3.94 (s, 2H), 3.87 (s, 3H), 3.57 (t, J=6.9 Hz, 3H), 2.04-1.95 (m, 5H), 1.84 (d, J=5.0 Hz, 2H), 1.77-1.57 (m, 7H), 1.55-1.50 (m, 11H); 19F NMR (471 MHz, CDCl3) δ: −112.2 (s, 1F).

Workup

  1. additionwere successively added
  2. customThe organic layer was separated
  3. washwashed with H2O (5×15 mL) and brine (15 mL) until the pH=7
  4. concentrationwas concentrated in vacuo
  5. customThe residual crude oil was purified by flash chromatography (SiO2)
  6. customfrom 0% to 30% EtOAc/hexane (10 min)

Sources & evidence

ORD record
ord-cb5843a97f6341d6ad9753b14eaf235c
Source dataset
uspto-grants-2015_02
Patent number
US08962660B2

Reaction notes

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