Trifluoroacetic anhydride → HCID 89462819, compound

An ice cooled suspension of 1-(4-fluorobenzyl)-1,4,6,7-tetrahydropyrano[4,3-b]pyrrole-2,3-dicarboxylic acid (3.1 g, 9.71 mmol) in Dichloromethane (DCM) (50 mL) was treated with TFAA (2.70 mL, 19.42 mmol) and warmed to ambient temperature. After 2 h, the reaction mixture was concentrated in vacuo, dissolved in MeOH (5 mL) and heated to reflux (90° C. bath). After 2 h, the reaction mixture was concentrated in vacuo to afford 1-(4-fluorobenzyl)-3-(methoxycarbonyl)-1,4,6,7-tetrahydropyrano[4,3-b]pyrrole-2-carboxylic acid. The crude acid was dissolved in DMF (25 mL) and treated with N-methyl sarcosine methyl ester HCl (2.033 g, 14.56 mmol), DIPEA (2.54 mL, 14.56 mmol) and HATU (4.43 g, 11.65 mmol). After 20 min, the reaction mixture was partitioned between water and EtOAc. The layers were separated and the organic phase was washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by ISCO (0-50% EtOAc-hexanes) to afford methyl 1-(4-fluorobenzyl)-2-((2-methoxy-2-oxoethyl)(methyl)carbamoyl)-1,4,6,7-tetrahydropyrano[4,3-b]pyrrole-3-carboxylate (3.2 g, 7.65 mmol, 79% yield) as a white solid. LCMS (m/z) ES+=419 (M+1).

1. concentrationthe reaction mixture was concentrated in vacuo
2. dissolutiondissolved in MeOH (5 mL)
3. temperatureheated
4. temperatureto reflux (90° C. bath)
5. waitAfter 2 h
6. concentrationthe reaction mixture was concentrated in vacuo

ORD record

ord-de0284d2d0d345169e698b1eebc270c7

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09012642B2