Formaldehyde → 2,7-Diazaspiro[3.5]nonane-2-carboxylic acid, 7-methyl-, 1,1-dimethylethyl ester
Reaction equation
Cl.[C:2]([O:6][C:7]([N:9]1[CH2:12][C:11]2([CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)[CH2:10]1)=[O:8])([CH3:5])([CH3:4])[CH3:3].C=O.[C:20](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].O>ClCCCl>[C:2]([O:6][C:7]([N:9]1[CH2:12][C:11]2([CH2:17][CH2:16][N:15]([CH3:20])[CH2:14][CH2:13]2)[CH2:10]1)=[O:8])([CH3:5])([CH3:3])[CH3:4]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of 2,7-diaza-spiro[3.5]nonane-2-carboxylic acid tert-butyl ester hydrochloride (100 mg, 0.381 mmol) in DCE (10 mL) was added an aqueous solution of formaldehyde (37% w/w, 40 μL, 0.537 mmol). The mixture was stirred at RT for 10 min, then sodium triacetoxyborohydride (121 mg, 0.571 mmol) was added and stirring was continued for 1 h. Water was added to the reaction mixture before being loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH then eluted with 2 M NH3 in MeOH to give 7-methyl-2,7-diaza-spiro[3.5]nonane-2-carboxylic acid tert-butyl ester. To a solution of 7-methyl-2,7-diaza-spiro[3.5]nonane-2-carboxylic acid tert-butyl ester in DCM (5 mL) was added TFA (1 mL) and the resulting mixture was stirred at RT for 1 h. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge, washed with MeOH then eluted with 2 M NH3 in MeOH to give the title compound as a colourless oil (45 mg, 84%).
Workup
- stirringstirring
- waitwas continued for 1 h
- washThe cartridge was washed with MeOH
- washthen eluted with 2 M NH3 in MeOH
Sources & evidence
- ORD record
- ord-6eb26b3965274a04974d029f28b9ff08
- Source dataset
- uspto-grants-2012_10
- Patent number
- US08293735B2
Reaction notes
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