Triethylamine → Tert-butyl 2,2-difluoro-4-(5-methylthiophene-2-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate

Temperatur

20 °C

HATU (0.541 g) was added in one portion to a stirred solution at 0° C. of tert-butyl 2,2-difluoro-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate (example 37, step c) (0.32 g) and 5-methylthiophene-2-carboxylic acid (0.171 g) and triethylamine (0.458 mL) in DMF (20 mL). The mixture was then stirred at 20° C. for 7 hours. The mixture was partitioned between ethyl acetate and brine, the organic layer was washed twice with brine, dried over sodium sulphate, filtered and the solvent evaporated under reduced pressure. The crude product was purified by flash silica chromatography, elution gradient 0.5 to 5% methanol in dichloromethane. Pure fractions were evaporated to dryness to afford the subtitled compound. Yield 0.4 g.

1. customThe mixture was partitioned between ethyl acetate and brine
2. washthe organic layer was washed twice with brine
3. dry with materialdried over sodium sulphate
4. filtrationfiltered
5. customthe solvent evaporated under reduced pressure
6. customThe crude product was purified by flash silica chromatography, elution gradient 0.5 to 5% methanol in dichloromethane
7. customPure fractions were evaporated to dryness

ORD-Eintrag

ord-144a35b2a9584e44ac3c53fb58a05a5e

Quelldatensatz

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08629271B2