Reaction #160214

Reaction equation

(8-benzyl-10-vinyl-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl)-(4-isopropoxy-3-methyl-phenyl)methanone

ozone

NaBH4

→

[8-benzyl-10-(hydroxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone

Yield 34.0%

Solvents

DCM

methanol

methanol

Conditions

Workup

1. 1
   workup.WAITat 0° C. for 1 hour
2. 2
   ConcentrationThe reaction mixture was concentrated in vacuo
3. 3
   Otherquenched with 4N HCl/dioxane
4. 4
   Concentrationconcentrated in vacuo
5. 5
   workup.ADDITIONdiluted with methanol-water (1:1)
6. 6
   Othermicrofiltered and purified by prep LCMS (1-99% ACN/Water, 5 mM HCl modifier)

Procedure

To (8-benzyl-10-vinyl-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl)-(4-isopropoxy-3-methyl-phenyl)methanone (135 mg, 0.30 mmol) in DCM (4 mL) and methanol (1 mL) at −78° C. was bubbled ozone until the solution turned faint blue. NaBH4 (91 mg, 2.41 mmol) and methanol (˜2 mL) was added under an atmosphere of nitrogen and the reaction mixture was stirred at −78° C. for 30 minutes, then at 0° C. for 1 hour. The reaction mixture was concentrated in vacuo, quenched with 4N HCl/dioxane, concentrated in vacuo, then diluted with methanol-water (1:1), microfiltered and purified by prep LCMS (1-99% ACN/Water, 5 mM HCl modifier) to give [8-benzyl-10-(hydroxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone (50 mg, 34%). ESI-MS m/z calc. 452.6. Found 453.5 (M+1)+; Retention time: 1.18 minutes (3 min run).

Source