tert-Butanol → 8-Benzyl-3-(4-isopropoxy-3-methyl-benzoyl)-11-oxa-3,8-diazaspiro[5.5]undecane-10-carboxylic acid

To [8-benzyl-10-(1,2-dihydroxyethyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone (1.53 g, 3.17 mmol) in THF (28 mL) was added NaIO4 (1.36 g, 6.34 mmol) followed by the addition of water (10 mL). The reaction mixture was stirred at room temperature for 2 hours, then filtered through celite, and concentrated in vacuo. The residue was partitioned between sat. aq. sodium bicarbonate (50 mL) and ethyl acetate (50 mL) and the aqueous layer was extracted further with ethyl acetate (3×50 mL). The organics were combined, washed with sat. aq. sodium bicarbonate (50 mL), dried over MgSO4, and concentrated in vacuo. To the intermediate aldehyde (˜1.4 g) was added 2-methylpropan-2-ol (17 mL) and 2-methylbut-2-ene (9 mL, 85.08 mmol) and the reaction mixture was cooled to 0° C. A solution of NaClO2 (938 mg, 8.29 mmol) and NaH2PO4 (1.15 g, 8.31 mmol) in water (17 mL) was added dropwise over 5 minutes, and the reaction mixture was stirred for 30 minutes. The reaction mixture was warmed to room temperature, then extracted with ethyl acetate (4×50 mL) and the combined organic layer was washed with brine (15 mL), dried over MgSO4, filtered and concentrated in vacuo to give 8-benzyl-3-(4-isopropoxy-3-methyl-benzoyl)-11-oxa-3,8-diazaspiro[5.5]undecane-10-carboxylic acid as a white foam (1.48 g, 100%). ESI-MS m/z calc. 466.6. found 467.5 (M+1)+; Retention time: 1.27 minutes (3 min run).

1. filtrationfiltered through celite
2. concentrationconcentrated in vacuo
3. customThe residue was partitioned between sat. aq. sodium bicarbonate (50 mL) and ethyl acetate (50 mL)
4. extractionthe aqueous layer was extracted further with ethyl acetate (3×50 mL)
5. washwashed with sat. aq. sodium bicarbonate (50 mL)
6. dry with materialdried over MgSO4
7. concentrationconcentrated in vacuo
8. temperaturethe reaction mixture was cooled to 0° C
9. stirringthe reaction mixture was stirred for 30 minutes
10. temperatureThe reaction mixture was warmed to room temperature
11. extractionextracted with ethyl acetate (4×50 mL)
12. washthe combined organic layer was washed with brine (15 mL)
13. dry with materialdried over MgSO4
14. filtrationfiltered
15. concentrationconcentrated in vacuo

ORD record

ord-2c3d18417f794073b7c802017f3d52a5

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09181273B2