Water → 1190391-97-9

A solution of the product from step A (4.92 g, 17.82 mmol) was dissolved in methanol (20 mL) and added dropwise to a mixture of 5 N NaOH (4.25 mL, 21.25 mmol), water (16 mL) and methanol (30 mL). After addition was complete the mixture was stirred for 2 h. The methanol was removed by evaporation and the pH of the remaining aqueous was adjusted to ˜2.5 with conc. HCl. The mixture was saturated with solid NaCl and extracted with EtOAc (x3); combined EtOAc layers washed with sat. NaCl, dried over Na2SO4 and treated with activated charcoal overnight. The filtered mixture was evaporated. The residue was triturated with EtOAc, and the solid filtered to give 1.94 g of the desired product. The mother liquors were evaporated and purified by MPLC using a gradient rising from 100% Hexanes to 100% EtOAc in Hexanes to give a further 0.82 g of the title product (2.76 g in total, 62%) as an off white solid. 1H NMR (500 MHz CDCl3) δ: 4.04 (m, 1H), 3.02-3.08 (m, 1H), 2.88-2.94 (m, 1H), 2.78-2.83 (m, 2H).

1. additionAfter addition
2. customThe methanol was removed by evaporation
3. extractionextracted with EtOAc (x3)
4. washcombined EtOAc layers washed with sat. NaCl
5. dry with materialdried over Na2SO4
6. additiontreated with activated charcoal overnight
7. customThe filtered mixture was evaporated
8. customThe residue was triturated with EtOAc
9. filtrationthe solid filtered

ORD record

ord-379898c6d13c42c0bcea183a861df45a

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08653260B2