Diisopropylethylamine → Tert-butyl 8-benzyl-9,9-dimethyl-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate

HRID 73050Notes

Reaction equation

HRID 73050 reaction equation
[CH2:1]([N:8]([CH2:14][C:15]1([OH:28])[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]1)[C:9]([CH3:13])([CH3:12])[CH2:10]O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.CS(OS(C)(=O)=O)(=O)=O>O1CCCC1.C(OCC)(=O)C>[CH2:1]([N:8]1[C:9]([CH3:13])([CH3:10])[CH2:12][O:28][C:15]2([CH2:16][CH2:17][N:18]([C:21]([O:23][C:24]([CH3:25])([CH3:26])[CH3:27])=[O:22])[CH2:19][CH2:20]2)[CH2:14]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 81560Methanesulfonic anhydrideHCID 70872650Tert-butyl 4-((benzyl(1-hydroxy-2-methylpropan-2-yl)amino)methyl)-4-hydroxypiperidine-1-carboxylate

Product 1

HCID 70872658Tert-butyl 8-benzyl-9,9-dimethyl-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylateYield 28.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of tert-butyl 4-[[benzyl-(2-hydroxy-1,1-dimethyl-ethyl)amino]methyl]-4-hydroxy-piperidine-1-carboxylate (330 mg, 0.841 mmol) in tetrahydrofuran was added N,N-diisopropylethylamine (439 μL, 2.52 mmol) and methanesulfonic anhydride (439 mg, 2.52 mmol) under a nitrogen atmosphere. The reaction mixture was heated at 65° C. for 18 h. The reaction mixture was diluted with ethyl acetate, washed with saturated sodium bicarbonate (2×50 mL) and brine (50 mL), dried over Na2SO4, filtered and concentrated in vacuo. The crude material was purified by silica gel chromatography (0-80% of ethyl acetate/hexanes) to provide tert-butyl 8-benzyl-9,9-dimethyl-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate (89 mg, 28%) as white solid. ESI-MS m/z calc. 374.5. Found 375.3 (M+1)+; Retention time: 1.30 minutes (3 min run).

Workup

  1. washwashed with saturated sodium bicarbonate (2×50 mL) and brine (50 mL)
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude material was purified by silica gel chromatography (0-80% of ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-9ccfee7aca074b5cb9237d2d795c8b27
Source dataset
uspto-grants-2014_09
Patent number
US08828996B2

Reaction notes

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