95 mmol 3 eq was added portion wise over 1 h to a suspension of 8a 120 mg 0 31 mmol 1 eq in thf 30 ml at 0 u00b0 c and the mixture was stirred at 0 5 u00b0 c for 5 h saturated aq nacl was added slowly the organic layer was separated and the aqueous layer was extracted with thf 2 times the combined organic layers were dried over anhy na2so4 concentrated filtered and purified by column chromatography to give compound 8 51 mg yield 46 as a pale yellow solid 1 hnmr cdcl3 300 mhz ppm u03b49 05 s 2h 8 01 s 1h 5 49 s 2h 4 93 m 1h 4 05 m 2h 3 91 m 4h 3 77 m 411 1 54 d 3h es ms m z 357 m h step 1 a mixture of 7d 3 63 g 10 9 mmol 1 eq 8 oxa 3 azabicyclo 3 2 1 octane hcl 1 96 g 13 08 mmol 1 2 eq and cs 2 co 3 10 69 g 32 8 mmol 3 eq in dmf 40 ml was stirred at 80 u00b0 c for 3 h the mixture was poured in to ice water the resulting solid was collected by filtration and washed with water to give compound 9a 2 4 g yield 54 as a white solid es ms m z 409 m h step 2 a mixture of 9a 2 4 g 5 9 mmol 1 0 eq in hcl ea 30 ml was stirred at 0 u00b0 c for 30 min the mixture was adjusted ph to 8 9 with aq nahco 3 and extracted with ethyl acetate 3 times the combined.