Tert-Butyl hypochlorite → Phenylmethyl 2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-3-hydroxy-8-azaspiro[4.5]decane-8-carboxylate

HRID 734227Notes

Reaction equation

HRID 734227 reaction equation
[C:1]([NH:8][C:9](=O)[O-])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C([O:16]Cl)(C)(C)C.[CH2:18]1[C:22]2([CH2:27][CH2:26][N:25]([C:28]([O:30][CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)=[O:29])[CH2:24][CH2:23]2)[CH2:21]C=[CH:19]1>C(O)CC.[OH-].[Na+]>[CH3:7][C:4]([O:3][C:1]([NH:8][CH:9]1[CH:19]([OH:16])[CH2:18][C:22]2([CH2:27][CH2:26][N:25]([C:28]([O:30][CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)=[O:29])[CH2:24][CH2:23]2)[CH2:21]1)=[O:2])([CH3:5])[CH3:6]

Participants

6

Reactant 3

HCID 521297Tert-Butyl hypochloriteHCID 57418545Boc-carbamateHCID 69055893Phenylmethyl 8-azaspiro[4.5]dec-2-ene-8-carboxylate

Product 1

HCID 69054060Phenylmethyl 2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-3-hydroxy-8-azaspiro[4.5]decane-8-carboxylateYield 103.6%

Reagents, catalysts & solvents 2

HCID 10311-PropanolSolvent2×HCID 14798Sodium HydroxideSolvent2×

Procedure

To a solution of Boc-carbamate (2.68 g, 22.9 mmol) in nPrOH (70 mL) at 25° C. was added an NaOH solution (32 mL, prepared from 900 mg of NaOH in 37 mL H2O) followed by tBuOCl (2.58 mL, 22.51 mmol). After 15 min, phenylmethyl 8-azaspiro[4.5]dec-2-ene-8-carboxylate (2 g, 7.4 mmol) in nPrOH (3 mL) was added followed by K2OsO2(OH)2 (109 mg, 0.295 mmol) dissolved in the remaining NaOH solution prepared above (5 mL). After 1 h, the solution was extracted with EtOAc, concentrated and purified via column chromatography (1-7% MeOH in DCM (1% NH4OH)) yielding the title compound (˜3.1 g, contaminated with residual Boc-carbamate) as a white solid: LCMS (ES) m/e 405 (M+H)+.

Workup

  1. customprepared above (5 mL)
  2. waitAfter 1 h
  3. extractionthe solution was extracted with EtOAc
  4. concentrationconcentrated
  5. custompurified via column chromatography (1-7% MeOH in DCM (1% NH4OH))

Sources & evidence

ORD record
ord-0f54e5cbb9a04e4f8dfa56cef40c880e
Source dataset
uspto-grants-2009_09
Patent number
US07592334B2

Reaction notes

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