Water → Tert-butyl 8-tert-butyl-10-(hydroxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate

HRID 72915Notes

Reaction equation

HRID 72915 reaction equation
[C:1]([N:5]1[CH2:22][CH:21]([CH:23]([OH:26])CO)[O:20][C:7]2([CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]2)[CH2:6]1)([CH3:4])([CH3:3])[CH3:2].I([O-])(=O)(=O)=O.[Na+].O.[BH4-].[Na+]>O1CCCC1.[Cl-].[Na+].O.C(OCC)(=O)C.CO.ClCCl>[C:1]([N:5]1[CH2:22][CH:21]([CH2:23][OH:26])[O:20][C:7]2([CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:17])([CH3:18])[CH3:19])=[O:14])[CH2:9][CH2:8]2)[CH2:6]1)([CH3:2])([CH3:3])[CH3:4]

Participants

9

Reactant 4

HCID 962WaterHCID 4311764Sodium borohydrideHCID 23667635Sodium periodate2×HCID 68291705Tert-butyl 8-tert-butyl-10-(1,2-dihydroxyethyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate

Product 1

HCID 70872649Tert-butyl 8-tert-butyl-10-(hydroxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylateYield 71.2%

Reagents, catalysts & solvents 4

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 21226129Dichloromethane methanolSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of tert-butyl 8-tert-butyl-10-(1,2-dihydroxyethyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate (1.10 g, 2.95 mmol) in tetrahydrofuran (22 mL) was added sodium periodate (1.58 g, 7.38 mmol) and water (8.0 mL), resulting in a thick white precipitate. The reaction mixture was heated at 40° C. for 3 h, then additional sodium periodate added (2.95 mmol) and the mixture stirred for 16 h. The reaction mixture was filtered through Celite and rinsed with tetrahydrofuran (30 mL). The filtrate solution was cooled to 0° C. and treated portion-wise with sodium borohydride (223 mg, 5.91 mmol) over 5 min. The reaction mixture was stirred for 30 min then diluted with brine (400 mL) and ethyl acetate (400 mL). The organic phase was separated and the aqueous phase extracted with ethyl acetate (3×100 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. Silica gel chromatography (80 g silica, 1-10% methanol/dichloromethane) provided tert-butyl 8-tert-butyl-10-(hydroxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate (720 mg, 2.10 mmol, 71%) as colorless oil. ESI-MS m/z calc. 342.3. Found 343.5 (M+1)+; Retention time: 0.89 minutes (3 min run).

Workup

  1. customresulting in a thick white precipitate
  2. filtrationThe reaction mixture was filtered through Celite
  3. washrinsed with tetrahydrofuran (30 mL)
  4. temperatureThe filtrate solution was cooled to 0° C.
  5. stirringThe reaction mixture was stirred for 30 min
  6. customThe organic phase was separated
  7. extractionthe aqueous phase extracted with ethyl acetate (3×100 mL)
  8. dry with materialThe combined organic layers were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d14f90c6d6c94730b67fdd2cfe54388b
Source dataset
uspto-grants-2014_09
Patent number
US08828996B2

Reaction notes

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