Trimethyl borate → (2-(Benzyloxy)-6-methoxy-4-(5-methyloxazol-2-yl)phenyl)boronic acid

HRID 579307Notes

Reaction equation

HRID 579307 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:18]2[O:19][C:20]([CH3:23])=[CH:21][N:22]=2)[CH:12]=[C:13]([O:16][CH3:17])[C:14]=1Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.[B:29](OC)([O:32]C)[O:30]C>C1COCC1>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:18]2[O:19][C:20]([CH3:23])=[CH:21][N:22]=2)[CH:12]=[C:13]([O:16][CH3:17])[C:14]=1[B:29]([OH:32])[OH:30])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 8470Trimethyl borateHCID 867106072-(3-(Benzyloxy)-4-bromo-5-methoxyphenyl)-5-methyloxazoleHCID 178418339Butyllithium

Product 1

HCID 86710608(2-(Benzyloxy)-6-methoxy-4-(5-methyloxazol-2-yl)phenyl)boronic acidYield 35.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 2-(3-(benzyloxy)-4-bromo-5-methoxyphenyl)-5-methyloxazole (197 mg, 0.526 mmol) in THF (1.3 mL) cooled to −78° C. was added n-butyl lithium (2.5 M in hexanes, 232 uL, 0.579 mmol). The solution was stirred for 15 minutes after which time trimethyl borate (235 uL, 2.11 mmol) was added and the solution was allowed to slowly warm to room temperature overnight. The reaction was quenched by addition of 0.1 M HCl and was diluted with ethyl acetate, washed with water, brine, dried over magnesium sulfate and concentrated. Flash column chromatography (12 g silica, 0-100% ethyl acetate in DCM over 30 column volumes) provided (2-(benzyloxy)-6-methoxy-4-(5-methyloxazol-2-yl)phenyl)boronic acid (63 mg) as a white foam. MS=340.1 (M+1). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.28-7.46 (m, 5H), 7.25 (d, J=1.01 Hz, 1H), 7.08 (br. s, 1H), 6.85 (d, J=1.01 Hz, 1H), 5.17 (s, 2H), 3.95 (s, 3H), 2.38 (d, J=1.52 Hz, 3H).

Workup

  1. additionwas added
  2. customThe reaction was quenched by addition of 0.1 M HCl
  3. additionwas diluted with ethyl acetate
  4. washwashed with water, brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-518a0589e80346108b6998c808575bfd
Source dataset
uspto-grants-2015_05
Patent number
US09040712B2

Reaction notes

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