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956828-47-0

(4-chloro-2-fluoro-phenyl)-carbaMic acid tert-butyl ester synthesis

2synthesis methods
24424-99-5 Synthesis
Di-tert-butyl dicarbonate

24424-99-5
833 suppliers
$13.50/25G

57946-56-2 Synthesis
4-Chloro-2-fluoroaniline

57946-56-2
340 suppliers
$12.00/25g

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Yield:956828-47-0 89%

Reaction Conditions:

in 1,4-dioxane; for 48 h;Reflux;

Steps:

17.1 Step-1: tert-Butyl(4-chloro-2-fluorophenyl)carbamate

A solution of 4-chloro-2-fluoroaniline (2 g, 13.74 mmol) and di-tert-butyl dicarbonate (6.4 mL, 27.6 mmol) in 1,4-dioxane (50 mL) was stirred at reflux for 2 days.
The solvent was then evaporated.
The resulting oil was diluted with MeOH, water, and aqueous ammonium hydroxide solution (10 mL each) and vigorously stirred for 45 minutes.
The organic lower layer was separated.
The organic material was diluted with EtOAc (50 mL), and washed with water (50 mL), 3.6% aqueous HCl solution (2*50 mL), saturated aqueous NaHCO3 solution (50 mL), and then again with water (2*50 mL).
The organic layer was dried (MgSO4), filtered, and evaporated under reduced pressure to provide tert-butyl(4-chloro-2-fluorophenyl)carbamate (3.0011 g, 12.22 mmol, 89% yield) as a reddish liquid that solidified on standing. 1H NMR (300 MHz, DMSO-d6): δ ppm 9.12 (s, 1H), 7.63 (t, J=8.65 Hz, 1H), 7.42 (dd, J=10.85, 2.35 Hz, 1H), 7.18-7.24 (m, 1H), 1.45 (s, 9H). LCMS (Method 1): m/z 246 [M+H]+.

References:

US2016/83365,2016,A1 Location in patent:Paragraph 0648; 0649; 0650