(R)-tert-butyl 3-(tosyloxyMethyl) pyrrolidine-1-carboxylate synthesis

Yield:330797-71-2 88.98%

Reaction Conditions:

Stage #1: tert-butyl (R)-3-hydroxymethylpyrrolidine-1-carboxylatewith triethylamine in dichloromethane at 0; for 0.5 h;
Stage #2: p-toluenesulfonyl chloride in dichloromethane at 20;

Steps:

A.1 Step 1: (R)-tert-butyl 3-(tosyloxymethyl)pyrrolidine-1-carboxylate

To a solution of (R)-tert-butyl 3 -(hydroxymethyl)pyrrolidine- 1 -carboxylate (2.8 g, 13.91 mmol) in DCM (50 mL) was added triethylamine (4.21 g, 41.73 mmol) at 0°C. After the mixture was stirred at 0°C for 30 mi 4-methylbenzene-1-sulfonyl chloride (3.98 g, 20.87 mmol) was added in portions, and the reaction was stirred at room temperature overnight. The mixture was poured into the ice water and extracted with EtOAc (100 mL x 2). The organic layers were dried over Na2SO4, filtered and concentrated to give a residue, which was purifiedby silica gel chromatography (PE: EtOAc = 100: ito 4: 1) to give (R)-tert-butyl 3- (tosyloxymethyl)pyrrolidine-1-carboxylate (4.4 g, 88.98% yield) as a white solid. LC-MS: m/z = 300 [M+H-56j.

References:

WO2017/27684,2017,A1 Location in patent:Paragraph 00162