Ozone → HCID 68311127, compound

HRID 73032Notes

Reaction equation

HRID 73032 reaction equation
[CH2:1]([N:8]1[CH2:31][CH:30]([CH:32]=C)[O:29][C:10]2([CH2:15][CH2:14][N:13]([C:16]([C:18]3[CH:23]=[CH:22][C:21]([O:24][CH:25]([CH3:27])[CH3:26])=[C:20]([CH3:28])[CH:19]=3)=[O:17])[CH2:12][CH2:11]2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O:34]=[O+][O-].[BH4-].[Na+]>C(Cl)Cl.CO>[CH2:1]([N:8]1[CH2:31][CH:30]([CH2:32][OH:34])[O:29][C:10]2([CH2:15][CH2:14][N:13]([C:16]([C:18]3[CH:23]=[CH:22][C:21]([O:24][CH:25]([CH3:26])[CH3:27])=[C:20]([CH3:28])[CH:19]=3)=[O:17])[CH2:12][CH2:11]2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 24823OzoneHCID 4311764Sodium borohydrideHCID 86672478HCID 86672478, compound

Product 1

HCID 68311127HCID 68311127, compoundYield 34%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

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).

Workup

  1. waitat 0° C. for 1 hour
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customquenched with 4N HCl/dioxane
  4. concentrationconcentrated in vacuo
  5. additiondiluted with methanol-water (1:1)
  6. custommicrofiltered and purified by prep LCMS (1-99% ACN/Water, 5 mM HCl modifier)

Sources & evidence

ORD record
ord-32ee2d5a14b94c9eb3c49206f057c138
Source dataset
uspto-grants-2014_09
Patent number
US08828996B2

Reaction notes

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