Trimethyl borate → (4-(2-((tert-Butyldimethylsilyl)oxy)-1,1-difluoroethyl)-3,5-dimethylphenyl)boronic acid

HRID 708807Notes

Reaction equation

HRID 708807 reaction equation
[Li]CCCC.Br[C:7]1[CH:12]=[C:11]([CH3:13])[C:10]([C:14]([F:25])([F:24])[CH2:15][O:16][Si:17]([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18])=[C:9]([CH3:26])[CH:8]=1.[B:27](OC)([O:30]C)[O:28]C>C1COCC1>[Si:17]([O:16][CH2:15][C:14]([C:10]1[C:11]([CH3:13])=[CH:12][C:7]([B:27]([OH:30])[OH:28])=[CH:8][C:9]=1[CH3:26])([F:25])[F:24])([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18]

Participants

5

Reactant 3

HCID 8470Trimethyl borateHCID 123422069(2-(4-Bromo-2,6-dimethylphenyl)-2,2-difluoroethoxy)(tert-butyl)dimethylsilaneHCID 178418339Butyllithium

Product 1

HCID 123846221(4-(2-((tert-Butyldimethylsilyl)oxy)-1,1-difluoroethyl)-3,5-dimethylphenyl)boronic acidYield 82%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

n-BuLi (1.6 M in hexanes, 1.236 ml, 1.977 mmol) was added to a solution of Intermediate 7C (500 mg, 1.318 mmol) in THF (5 ml) at −78° C. After 45 min, trimethyl borate (0.295 ml, 2.64 mmol) was added and the cooling bath was removed. The reaction mixture was warmed to rt, diluted with diethyl ether (300 mL), washed with 1.0 HCl, water and brine and concentrated. The crude product was purified by flash chromatography (loading in chloroform, 0 to 100% ethyl acetate in hexane over 30 min using a 12 g Isco column). Intermediate 7D (370 mg, 82% yield) was obtained as a white solid. 1H NMR (400 MHz, chloroform-d) δ ppm −0.03-0.02 (m, 6H) 0.82-0.88 (m, 9H) 2.57-2.63 (m, 6H) 4.10 (t, J=12.92 Hz, 2H) 7.86 (s, 2H).

Workup

  1. customthe cooling bath was removed
  2. additiondiluted with diethyl ether (300 mL)
  3. washwashed with 1.0 HCl, water and brine
  4. concentrationconcentrated
  5. customThe crude product was purified by flash chromatography (loading in chloroform
  6. wait0 to 100% ethyl acetate in hexane over 30 min using

Sources & evidence

ORD record
ord-0da46e1ab0394d13ad21472f83cf0610
Source dataset
uspto-grants-2015_11
Patent number
US09174974B2

Reaction notes

Loading…