Diisopropylethylamine → Tert-butyl 8-[(4-methoxyphenyl)methyl]-9-phenyl-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate

HRID 72891Notes

Reaction equation

HRID 72891 reaction equation
[OH:1][C:2]1([CH2:15][N:16]([CH:26]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:27]O)[CH2:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.CCN(C(C)C)C(C)C.CS(OS(C)(=O)=O)(=O)=O>C1COCC1>[CH3:25][O:24][C:21]1[CH:22]=[CH:23][C:18]([CH2:17][N:16]2[CH:26]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH2:27][O:1][C:2]3([CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:12])[CH3:13])=[O:9])[CH2:4][CH2:3]3)[CH2:15]2)=[CH:19][CH:20]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 81560Methanesulfonic anhydrideHCID 70872871Tert-butyl 4-hydroxy-4-[[(2-hydroxy-1-phenyl-ethyl)-[(4-methoxyphenyl)methyl]amino]methyl]piperidine-1-carboxylate

Product 1

HCID 70872472Tert-butyl 8-[(4-methoxyphenyl)methyl]-9-phenyl-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylateYield 51.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of tert-butyl 4-hydroxy-4-[[(2-hydroxy-1-phenyl-ethyl)-[(4-methoxyphenyl)methyl]amino]methyl]piperidine-1-carboxylate (1.0 g, 2.13 mmol) in THF (10 mL) was added DIEA (1.1 mL, 6.38 mmol) followed by an addition of a solution of methylsulfonyl methanesulfonate (1.1 g, 6.38 mmol) in THF (2 mL) under an atmosphere of nitrogen at 0° C. The reaction mixture was warmed to room temperature and then heated at 40° C. for 16 hours. The reaction mixture was quenched with water and the aqueous layer was extracted with DCM. The organic layer was washed with a sat. solution of NaHCO3, followed by washing with water. The organic layer was dried over MgSO4 and concentrated in vacuo. The residue was purified by silica gel column chromatography using 0 to 100% DCM in hexanes as eluent to obtain tert-butyl 8-[(4-methoxyphenyl)methyl]-9-phenyl-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate (0.5 g, 51%). ESI-MS m/z calc. 452.6. Found 453.5 (M+1)+; Retention time: 1.62 minutes (3 min run).

Workup

  1. temperatureheated at 40° C. for 16 hours
  2. customThe reaction mixture was quenched with water
  3. extractionthe aqueous layer was extracted with DCM
  4. washThe organic layer was washed with a sat. solution of NaHCO3
  5. washby washing with water
  6. dry with materialThe organic layer was dried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-3dccc4a736a34012a238265ce5d4ab63
Source dataset
uspto-grants-2014_09
Patent number
US08828996B2

Reaction notes

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