tert-butyl 4-(2-chloro-5-fluorophenoxy)piperidine-1-carboxylate synthesis
- Product Name:tert-butyl 4-(2-chloro-5-fluorophenoxy)piperidine-1-carboxylate
- CAS Number:944808-10-0
- Molecular formula:C16H21ClFNO3
- Molecular Weight:329.79
3827-49-4
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Yield:944808-10-0 53%
Reaction Conditions:
with caesium carbonate in N,N-dimethyl-formamide at 70; for 24 h;
Steps:
8.b
b) 4- (2-chloro-5-fluoro-phenoxy) -piperidine (8b) 9g (44.7mmol) of BOC-4-hydroxy-piperidine are placed in 3OmL of dichloromethane at 00C. 3.5 mL (44.7mmol) of mesyl chloride and 8mL (58.1mmol) of triethylamine are slowly added. The reaction medium is stirred for 3h at 00C, and then filtered on a frit. The filtrate is washed with water. After drying on MgSO4, the organic phase is concentrated. 12.48g of oil are obtained (quantitative yield) . TLC silica gel 60 F 254 Merck, CH2Cl2-MeOH: 95-5, Rf=O.60. 1.34 g (4.78mmol) of this oil is placed in the presence of 0.50 mL (2.48 mmol) of 2-chloro-5-fluorophenol and of 3g (4.78mmol) of cesium carbonate in 5mL of DMF. This solution is stirred for 24h at 700C. After concentration of the reaction medium, the obtained residue is purified by flash chromatography (petroleum ether-AcOEt, gradient 100-0 to 85-15 over 60 min) . 0.84g of clear oil is obtained (yield: 53%) . TLC silica gel 60 F 254 Merck, CH2Cl2-AcOEt: 95-5, Rf=O.72. This oil is placed in 5mL of CH2Cl2 in the presence of 0.76 mL (10.2mmol) of TFA. The solution is stirred for 6h at room temperature. After concentration of the reaction medium, the residue is taken up with AcOEt, washed with a soda (IN) solution and then with NaCl saturated water. After drying the organic phase on MgSO4, 0.4g of intermediate 8b is obtained as a clear oil (yield 69%) . TLC silica gel 60 F 254 Merck, CH2Cl2-MeOH: 95-5, Rf=O.19.
References:
WO2010/6962,2010,A1 Location in patent:Page/Page column 29
3827-49-4
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109384-19-2
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944808-10-0
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109384-19-2
473 suppliers
$5.00/1g
944808-10-0
1 suppliers
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