Triphenylphosphine → Diethyl 1-((1-((tert-butoxycarbonyl)amino)cyclopropyl)methyl)-3-iodo-1H-pyrazole-4,5-dicarboxylate

Temperatur

0 °C

To a stirred solution of PPh3 (15.52 g, 59.2 mmol) in THF (80.0 mL) cooled to 0° C. was added DIAD (11.50 mL, 59.2 mmol) and the resulting solution stirred at 0° C. for 0.5 h. Intermediate 104C (8.00 g, 23.66 mmol) was added as a solution in THF (20 mL) at 0° C. and stirred at RT for 45 min. A solution of tert-butyl (1-(hydroxymethyl)cyclopropyl)carbamate (5.32 g, 28.4 mmol) in THF (10 mL) at was added at 0° C. and the reaction mixture was allowed to stir at RT for 16 h. The reaction mixture was diluted with water (250 mL) and extracted with EtOAc (2×200 mL). The combined organic layer was washed with brine dried over Na2SO4, filtered and concentrated. The crude product was purified by silica gel chromatography (220 g REDISEP® column, eluting with 20% EtOAc in hexane). Fractions containing the product were combined and evaporated to afford Intermediate 350A as a pale yellow liquid (10 g, 85%). MS(ES): m/z=508 [M+H]+; 1H NMR (400 MHz, chloroform-d) δ ppm 4.45 (s, 2H), 4.41-4.25 (m, 4H), 1.46 (s, 9H), 1.40-1.30 (m, 4H), 1.24 (s, 3H), 1.03-0.94 (m, 2H), 0.90-0.78 (m, 2H).

1. stirringstirred at RT for 45 min
2. stirringto stir at RT for 16 h
3. extractionextracted with EtOAc (2×200 mL)
4. washThe combined organic layer was washed with brine
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. customThe crude product was purified by silica gel chromatography (220 g REDISEP® column, eluting with 20% EtOAc in hexane)
9. additionFractions containing the product
10. customevaporated

ORD-Eintrag

ord-1fea88af7f0946d9bd8922390cc10044

Quelldatensatz

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09273058B2