Toluene → tert-Butyl 3-cyclopropyl-4-fluorobenzylcarbamate

HRID 1093043Notes

Reaction equation

HRID 1093043 reaction equation
[C:1]1([CH3:7])C=CC=C[CH:2]=1.Br[C:9]1[CH:10]=[C:11]([CH:21]=[CH:22][C:23]=1[F:24])[CH2:12][NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17].[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(B(O)O)CC1>O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:7]1([C:9]2[CH:10]=[C:11]([CH:21]=[CH:22][C:23]=2[F:24])[CH2:12][NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH2:1][CH2:2]1

Participants

7

Reactant 4

HCID 1140TolueneHCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 21961437[(3-Bromo-4-fluorophenyl)methyl]-carbamic acid tert-butyl ester

Product 1

HCID 57905173tert-Butyl 3-cyclopropyl-4-fluorobenzylcarbamateYield 88%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent2×

Conditions

Temperature
100 °C

Procedure

Under N2, a toluene (4.70 mL)/water (0.235 mL) solution of tert-butyl 3-bromo-4-fluorobenzylcarbamate (0.300 g, 0.986 mmol) was treated with potassium phosphate tribasic (0.733 g, 3.45 mmol), cyclopropylboronic acid (0.110 g, 1.282 mmol), and tricyclohexenylphosphene (0.028 g, 0.099 mmol) in was added palladium(II) acetate (0.011 g, 0.049 mmol). The reaction was stirred at 100° C. for 3 h. The solution was diluted with water (15 mL) then extracted with ethyl acetate (2×15 mL). The organic extracts were combined, washed with brine (20 mL), then dried (MgSO4), filtered and concentrated. The residue was purified by flash chromatography (Biotage flash chromatography system; 60 g SiO2; 0-20% ethyl acetate:hexane over 900 mL) to give the title compound as a white crystalline solid (0.230 g, 88% yield). 1H NMR (500 MHz, CDCl3) δ: 6.98-7.05 (1 H, m), 6.90-6.97 (1 H, m), 6.79 (1 H, dd, J=7.02, 1.53 Hz), 4.75 (1 H, brs), 4.21 (2 H, d, J=5.49 Hz), 2.02-2.09 (1 H, m), 1.45 (9 H, s), 0.93-1.01 (2 H, m), 0.66-0.75 (2 H, m).

Workup

  1. extractionthen extracted with ethyl acetate (2×15 mL)
  2. washwashed with brine (20 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography (Biotage flash chromatography system; 60 g SiO2; 0-20% ethyl acetate:hexane over 900 mL)

Sources & evidence

ORD record
ord-0233b4f045794367a37796fd52eecf5f
Source dataset
uspto-grants-2012_03
Patent number
US08129398B2

Reaction notes

Loading…