Lithium diisopropylamide → 4-[1-(3-Bromo-5-methoxymethyl-thiophen-2-yl)-methanoyl]-piperidine-1-carboxylic acid tert-butyl ester

温度

-78 °C

Add lithium diisopropyl amide (13.20 mL, 26.37 mmol, 1.05 equivalents) to a stirred, cold (−78° C.) solution of 4-bromo-2-methoxymethyl-thiophene (5.20 g, 25.11 mmol, 1.00 equivalents) in tetrahydrofuran (dry, 24.30 mL). Stir at −78° C. for 1 hour and add a solution of 4-(methoxy-methyl-carbamoyl)-piperidine-1-carboxylic acid tert-butyl ester (6.84 g, 25.11 mmol, 1.00 equivalents) in tetrahydrofuran (dry, 16.40 mL), dropwise. Stir the resulting solution at −78° C. for 3 hours. Quench the reaction mixture with saturated sodium chloride (aqueous, 50 mL). Allow the resulting mixture to warm to room temperature and extract with a mixture of ethyl acetate: diethyl ether (1:1, 3×35 mL). Combine the extracts, dry over magnesium sulfate, filter and evaporate. Purify the residue via flash column chromatography eluting with a mixture of n-heptane: ethyl acetate (4:1) to yield the desired product as a yellow oil (9.47 g). LC/MS (ESI), m/e 362 (M-56) and 418 (MH+), retention time 2.08 minutes. Condition II.

1. stirringStir the resulting solution at −78° C. for 3 hours
2. customQuench the reaction mixture with saturated sodium chloride (aqueous, 50 mL)
3. temperatureto warm to room temperature
4. extractionextract with a mixture of ethyl acetate: diethyl ether (1:1, 3×35 mL)
5. dry with materialCombine the extracts, dry over magnesium sulfate
6. filtrationfilter
7. customevaporate
8. customPurify the residue via flash column chromatography
9. washeluting with a mixture of n-heptane: ethyl acetate (4:1)

ORDレコード

ord-201644ecceec4db5a7aba1587d44016b

出典データセット

uspto-grants-2007_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07186724B2