2-[3-(tert-Butyldimethylsilanyloxy)propyl]thiazole → 7-{2-[3-(tert-Butyldimethylsilanyloxy)propyl]thiazol-5-yl}-3,9-diaza-bicyclo[3.3.1]non-6-ene-3,6,9-tricarboxylic acid 3,9-di-tert-butyl ester 6-methyl ester

温度

-78 °C

BuLi (1.6 M in hexane, 5.7 mL, 9.1 mmol) was added dropwise to a sol. of 2-[3-(tert-butyldimethylsilanyloxy)propyl]thiazole (1.80 g, 6.79 mmol) in THF (15 mL) at −78° C. The reaction mixture was stirred at −78° C. for 1 h, and ZnCl2 (1M in THF, 11.3 mL, 11.3 mmol) was added dropwise at −78° C. The cooling bath was then removed and the reaction stirred for 1 h while warming up to rt. A sol. of compound Y (2.00 g, 3.77 mmol) in THF (5 mL) was added dropwise, followed by Pd(PPh3)4 (126 mg, 0.109 mmol). The reaction mixture was stirred at rt for 2 h, then partitioned between EtOAc and aq. 1M NaOH, and the layers were separated. The aq. layer was extracted with EtOAc. The combined org. layers were washed with brine, dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification by FC (heptane/EtOAc= 7/3) yielded the title compound (1.75 g, 73%). LC-MS: tR=1.20 min, ES+: 638.35.

1. customThe cooling bath was then removed
2. stirringthe reaction stirred for 1 h
3. temperaturewhile warming up to rt
4. stirringThe reaction mixture was stirred at rt for 2 h
5. custompartitioned between EtOAc and aq. 1M NaOH
6. customthe layers were separated
7. extractionThe aq. layer was extracted with EtOAc
8. washlayers were washed with brine
9. dry with materialdried over MgSO4
10. filtrationfiltered
11. customthe solvents were removed under reduced pressure
12. customPurification by FC (heptane/EtOAc= 7/3)

ORDレコード

ord-eca7b4e75d83483dacb66c00ad0b1b61

出典データセット

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08138340B2