Triisopropyl borate → 2-(Neopentyloxycarbonyl)-5-(trifluoromethyl)phenylboronic acid

HRID 277454Notes

Reaction equation

HRID 277454 reaction equation
[CH3:1][C:2]([CH3:18])([CH3:17])[CH2:3][O:4][C:5](=[O:16])[C:6]1[CH:11]=[CH:10][C:9]([C:12]([F:15])([F:14])[F:13])=[CH:8][CH:7]=1.C([O:22][B:23](OC(C)C)[O:24]C(C)C)(C)C.C([N-]C(C)C)(C)C.[Li+]>O1CCCC1.O1CCCC1.CCCCCCC>[CH3:1][C:2]([CH3:18])([CH3:17])[CH2:3][O:4][C:5]([C:6]1[CH:11]=[CH:10][C:9]([C:12]([F:13])([F:14])[F:15])=[CH:8][C:7]=1[B:23]([OH:24])[OH:22])=[O:16]

Participants

6

Reactant 3

HCID 21531Triisopropyl borateHCID 599219Neopentyl 4-(trifluoromethyl)benzoateHCID 2724682Lithium diisopropylamide

Product 1

HCID 154622682-(Neopentyloxycarbonyl)-5-(trifluoromethyl)phenylboronic acidYield 62%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 21263495Tetrahydrofuran heptaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 4-trifluoromethyl-benzoic acid 2,2-dimethyl-propyl ester (4.225 g, 16.23 mmol) in tetrahydrofuran (40 mL) was added triisopropylborate (9.00 mL, 39.0 mmol). The solution was cooled to −78° C. and lithium diisopropylamide (12.0 mL of a 2.0 M solution in tetrahydrofuran/heptane, 24.0 mmol) was added dropwise over 5 minutes. The red solution was stirred for 30 minutes, warmed to 0° C., and quenched by the slow addition of 1N hydrochloric acid (50 mL). The mixture was allowed to warm to room temperature, stirred for 30 minutes and added to hexanes (200 mL). The layers were separated and the organic layer was washed successively with 2N hydrochloric acid (two times with 100 mL), water (100 mL), and brine (50 mL). The organic extracts were dried over magnesium sulfate, filtered, and concentrated to an oil. The crude product was crystallized from heptane (40 mL) to provide 2-(2,2-dimethyl-propoxycarbonyl)-5-trifluoromethyl-benzeneboronic acid (3.037 g, 62% yield) as a white solid: mp=159-160° C.; IR 3377 (br), 2963, 1703, 1371, 1308, 1171, 1131, 794, 709 cm−1; 1H NMR (400 MHz, DMSO/D2O) δ8.05 (d, J=8.1 Hz, 1H), 7.78 (d, J=8.3 Hz, 1H), 7.66 (s, 1H), 3.94 (s, 2H), 0.95 (s, 9H); 13C NMR (100 MHz, DMSO/D2O) δ26.69, 31.69, 74.91, 125.29, 125.75, 128.30, 129.62, 131.98 (q, J=31.8 Hz), 136.28, 142.68,166.90.

Workup

  1. temperaturewarmed to 0° C.
  2. customquenched by the slow addition of 1N hydrochloric acid (50 mL)
  3. temperatureto warm to room temperature
  4. stirringstirred for 30 minutes
  5. additionadded to hexanes (200 mL)
  6. customThe layers were separated
  7. washthe organic layer was washed successively with 2N hydrochloric acid (two times with 100 mL), water (100 mL), and brine (50 mL)
  8. dry with materialThe organic extracts were dried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated to an oil
  11. customThe crude product was crystallized from heptane (40 mL)

Sources & evidence

ORD record
ord-2a313e8232cb4f05909ae83206850e8f
Source dataset
uspto-grants-2002_03
Patent number
US06355825B1

Reaction notes

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