Trimethyl borate → HCID 71270813, compound

A suspension of 4-cyclopropyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one hydrochloride (4.05 mmol) in dichloromethane (10 mL) was treated with 1N aq NaOH (10.00 mmol) and was allowed to stir for 1 h, during which time the organic layer turned clear. The organic layer was partitioned from the aqueous layer, which was subsequently extracted with dichloromethane four times. The dichloromethane layers were combined, dried over sodium sulfate, filtered and concentrated in vacuo. This resulting residue was dissolved in dimethyl sulfoxide (7 mL) and was treated with 4-bromo-2-fluorobenzaldehyde (6.08 mmol), tert-butyl((1-methoxyvinyl)oxy)dimethylsilane (6.08 mmol) and trimethyl borate (8.11 mmol). The reaction was allowed to stir at room temperature for two days. At this point the reaction was slowly quenched with water (20 mL) and was stirred for one hour at room temperature. The solution was then extracted three times with ethyl acetate. The organic layers were combined, washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by silica gel chromatography (0-7% methanol/dichloromethane). The fractions containing the desired product were selected and concentrated in vacuo. The resulting oil was taken up in ethyl acetate (100 mL) and was washed three times with 30% w/v aq ammonium hydroxide, washed with brine, dried over sodium sulfate, filtered and concentrated to dryness in vacuo. The resulting oil was taken up in dichloromethane and concentrated to dryness in vacuo again to afford the title compound as a clear oil (1.148 g, 57% yield). MS(ES)+ m/e 469.2/471.2 [M+H]+ (bromide isotope pattern).

1. customThe organic layer was partitioned from the aqueous layer, which
2. extractionwas subsequently extracted with dichloromethane four times
3. dry with materialdried over sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. dissolutionThis resulting residue was dissolved in dimethyl sulfoxide (7 mL)
7. stirringto stir at room temperature for two days
8. customAt this point the reaction was slowly quenched with water (20 mL)
9. stirringwas stirred for one hour at room temperature
10. extractionThe solution was then extracted three times with ethyl acetate
11. washwashed with brine
12. dry with materialdried over sodium sulfate
13. filtrationfiltered
14. concentrationconcentrated in vacuo
15. customThe crude product was purified by silica gel chromatography (0-7% methanol/dichloromethane)
16. additionThe fractions containing the desired product
17. concentrationconcentrated in vacuo
18. washwas washed three times with 30% w/v aq ammonium hydroxide
19. washwashed with brine
20. dry with materialdried over sodium sulfate
21. filtrationfiltered
22. concentrationconcentrated to dryness in vacuo
23. concentrationconcentrated to dryness in vacuo again

ORD record

ord-222628514d894c329839d5ce9c1dcc02

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09084794B2