Sodium Carbonate → (S)-methyl 2-(2-(3-bromophenyl)-7-chloro-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of methyl 2-(2-(3-bromophenyl)-7-chloro-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetate (14 g, 34.3 mmol) in anhydrous toluene (400 mL) was added 1.1M (R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole/toluene (12.5 mL, 13.7 mmol). The mixture was cooled to −35° C. and then a 4.17M solution of catechoborane/toluene (11.7 mL, 48 mmol) was added over the course of 10 min. After 30 min, the reaction mixture was slowly warmed to −15° C. and stirred for additional 2 h. At this point the reaction mixture was diluted with EtOAc (300 mL) and treated with sat.aq. Na2CO3 (50 mL). The mixture was stirred vigorously for 10 min. The organic phase was separated and washed with sat. aq. Na2CO3 (5×100 mL), 0.1N HCl (1×100 mL), and brine. The organic phase was dried (Na2SO4), filtered, and concentrated. The residue was triturated with ether to obtain 12 g (77%) of the desired (S)-methyl 2-(2-(3-bromophenyl)-7-chloro-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 8.20 (t, J=1.8 Hz, 1H), 7.95 (dq, J=7.8, 0.8 Hz, 1H), 7.57 (ddd, J=8.0, 2.0, 1.0 Hz, 1H), 7.37 (t, J=7.9 Hz, 1H), 6.95 (s, 1H), 5.79 (s, 1H), 3.87 (s, 3H), 3.59 (d, J=1.8 Hz, 1H), 2.65 (s, 3H). LCMS (M+H)=410 and 412.

Provenance & Evidence