Formaldehyde → tert-butyl (6S,7S)-5-methyl-6-{[4-(3-methylphenyl)piperazin-1-yl]carbonyl}-5-azaspiro[2.5]octane-7-carboxylate

A mixture of (6S,7S)-7-(tert-butoxycarbonyl)-5-azaspiro[2.5]octane-6-carboxylic acid of step 1g (25 mg), BOP (45 mg), 1-(3-methylphenyl)piperazine (176 mg) and di-isopropylethylamine (70 μL) in DMF (500 μL) was stirred at RT overnight. Formaldehyde solution (0.5 M in THF/MeCN (1:1), 600 μL) was added to the mixture followed by NaBH(OAc)3 (0.25 M in THF/MeCN (1:1), 1000 μL). The resulting mixture was stirred overnight. The solvents were removed under reduced pressure. The residue was dissolved in ethyl acetate (5 mL). The solution was washed with NaHCO3 (7.5%, 3×1 mL). The organic phase was dried over MgSO4 and filtered and concentrated. The residue was used directly in the next step reaction without further purification.

1. stirringThe resulting mixture was stirred overnight
2. customThe solvents were removed under reduced pressure
3. dissolutionThe residue was dissolved in ethyl acetate (5 mL)
4. washThe solution was washed with NaHCO3 (7.5%, 3×1 mL)
5. dry with materialThe organic phase was dried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated
8. customThe residue was used directly in the next step reaction without further purification

ORD record

ord-d92a9c8898594f1baa192f903e123864

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09403775B2