Formic Acid → 2-Azatricyclo[3.3.1.13,7]decane-5-carboxylic acid, methyl ester

Temperature

60 °C

To 2-azatricyclo[3.3.1.13,7]decan-5-ol (Intermediate-7) (1.5 g, 5.9 mmol, 1 eq), 98% formic acid (9 ml) was added drop wise with vigorous gas evolution for over 30 minutes to a rapidly stirred 30% oleum (36 ml) heated to 60° C. Upon completion of this addition, 99% formic acid (9 ml) was slowly added for the next 30 minutes. The reaction mixture was stirred for another 1 hr at 60° C. (monitored by LCMS). The reaction mixture thus formed was then slowly poured into vigorously stirred methanol (75 ml) cooled to 00° C. The mixture was allowed to slowly warm to room temperature while stirring the reaction mixture for 4-5 hrs. The mixture was then concentrated under vacuum. The residue was poured into ice (30 g) and basified with saturated Na2CO3 solution. The aqueous layer was extracted with 5% methanol in DCM (3×100 ml). Combined organic layer was washed with brine and dried over Na2SO4. The organic layer was finally concentrated to get intermediate-8, (550 mg, 50% yield) as an oily mass.

1. additionwas slowly added for the next 30 minutes
2. customThe reaction mixture thus formed
3. temperaturecooled to 00° C
4. temperatureto slowly warm to room temperature
5. stirringwhile stirring the reaction mixture for 4-5 hrs
6. concentrationThe mixture was then concentrated under vacuum
7. additionThe residue was poured into ice (30 g)
8. extractionThe aqueous layer was extracted with 5% methanol in DCM (3×100 ml)
9. washCombined organic layer was washed with brine
10. dry with materialdried over Na2SO4
11. concentrationThe organic layer was finally concentrated
12. customto get intermediate-8

ORD record

ord-25e8b92db2bc4bee8b57c1a676c36855

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09303016B2