Triethylamine → (9-(2-Fluoro-3-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(5-isopropylthiophen-2-yl)methanone

O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.2 g) was added to a solution of 2-(3-(1-oxa-4,9-diazaspiro[5.5]undecan-9-ylmethyl)-2-fluorophenyl)ethanol (example 67, step f) (0.13 g), 5-isopropylthiophene-2-carboxylic acid (0.07 g) and triethylamine (0.23 mL) in DMF (7 mL) at 0° C. The resulting yellow solution was allowed to warm to RT and was stirred for 2 h. The mixture was partitioned between ethyl acetate (100 mL) and brine (100 mL), the organic phase was washed with brine (2×100 mL), dried over sodium sulphate, filtered and the solvent evaporated. The resulting gum was purified by silica gel chromatography eluting with 47.5:47.5:5 isohexane:ethyl acetate:triethylamine to 95:5 ethyl acetate:triethylamine gradient. The fractions containing product were combined, toluene (200 mL) was added, and the solvent evaporated to give the subtitled compound as a clear gum. Yield 0.23 g.

1. customThe mixture was partitioned between ethyl acetate (100 mL) and brine (100 mL)
2. washthe organic phase was washed with brine (2×100 mL)
3. dry with materialdried over sodium sulphate
4. filtrationfiltered
5. customthe solvent evaporated
6. customThe resulting gum was purified by silica gel chromatography
7. washeluting with 47.5:47.5:5 isohexane
8. additionThe fractions containing product
9. additiontoluene (200 mL) was added
10. customthe solvent evaporated

ORDレコード

ord-fa159ca612244c0086d131b2e008b3cd

出典データセット

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08148373B2