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

HRID 72903Notes

Reaction equation

HRID 72903 reaction equation
C([N:8]1[CH2:25][CH:24]([CH2:26][OH:27])[O:23][C:10]2([CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]2)[CH2:9]1)C1C=CC=CC=1.C([O-])=O.[NH4+]>CO.[OH-].[OH-].[Pd+2]>[OH:27][CH2:26][CH:24]1[O:23][C:10]2([CH2:11][CH2:12][N:13]([C:16]([O:18][C:19]([CH3:21])([CH3:20])[CH3:22])=[O:17])[CH2:14][CH2:15]2)[CH2:9][NH:8][CH2:25]1

Participants

5

Reactant 2

HCID 2723923Ammonium formate2×HCID 70872728Tert-butyl 8-benzyl-10-(hydroxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate

Product 1

HCID 70872648Tert-butyl 10-(hydroxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylateYield 90%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of tert-butyl 8-benzyl-10-(hydroxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate (2.00 g, 5.31 mmol) in methanol (38 mL) was added Pd(OH)2 (671 mg, 4.78 mmol) and ammonium formate (4.02 g, 63.7 mmol) and the mixture heated at 50° C. for 1 h. Additional catalyst (2.6 mmol) and ammonium formate (25 mmol) were added and the reaction heated for an additional 2 h. The reaction mixture was filtered and concentrated to ˜10 mL volume. The concentrate was diluted with dichloromethane and saturated sodium bicarbonate solution. The organic layer was separated and the aqueous layer washed with dichloromethane (5×50 mL). The combined organics were dried over Na2SO4, filtered, and concentrated to provide tert-butyl 10-(hydroxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate (1.37 g, 4.77 mmol, 90%) as an amber-colored glass. ESI-MS m/z calc. 286.2. Found 287.3 (M+1)+; Retention time: 0.65 minutes (3 min run).

Workup

  1. temperaturethe reaction heated for an additional 2 h
  2. filtrationThe reaction mixture was filtered
  3. concentrationconcentrated to ˜10 mL volume
  4. additionThe concentrate was diluted with dichloromethane and saturated sodium bicarbonate solution
  5. customThe organic layer was separated
  6. washthe aqueous layer washed with dichloromethane (5×50 mL)
  7. dry with materialThe combined organics were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-2e37ab4314c1472ab964ef4e30315d15
Source dataset
uspto-grants-2014_09
Patent number
US08828996B2

Reaction notes

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