反应详情

To a solution of crude 1-(tert-butoxycarbonylamino-methyl)-spiro[2.5]octane-1-carboxylic acid methyl ester (35.0 g, ˜96.2 mmol) was added LiOH—H2O (12.3 g, 294 mmol) followed by the addition of water (75 mL). The mixture was heated to reflux. After 48 hours, an additional portion of LiOH—H2O (6.15 g, 146 mmol) was added and refluxed for an additional 24 hours. The solvent was removed under reduced vacuum. The residue was partitioned between water and ether. The aqueous layer was acidified to pH 2–3 with aqueous HCl with ice bath cooling with a layer of CH2Cl2 present. The layers were separated and the aqueous layer was extracted with CH2Cl2 (3 times). The combined organic layers were dried over sodium sulfate, filtered and evaporated to give 17.0 g (63%, 2 steps) of 1-(tert-butoxycarbonylamino-methyl)-spiro[2.5]octane-1-carboxylic acid an off-white solid.

1. temperatureThe mixture was heated to reflux
2. temperaturerefluxed for an additional 24 hours
3. customThe solvent was removed under reduced vacuum
4. customThe residue was partitioned between water and ether
5. customThe aqueous layer was acidified to pH 2–3 with aqueous HCl with ice bath
6. temperaturecooling with a layer of CH2Cl2 present
7. customThe layers were separated
8. extractionthe aqueous layer was extracted with CH2Cl2 (3 times)
9. dry with materialThe combined organic layers were dried over sodium sulfate
10. filtrationfiltered
11. customevaporated