反应详情

4-(4-Chlorophenyl)-4-(methoxyimino)butanoic acid (Intermediate 53) (6.43 g, 26.61 mmol) in tetrahydrofuran (30 mL) was cooled, under an atmosphere of nitrogen, in an ice-methanol bath. Borane-tetrahydrofuran complex (1.0M in THF) (93 mL, 93.12 mmol) was added dropwise over a period of 20 minutes. The resulting solution was allowed to warm to room temperature, stirred for 1 hour then heated at reflux for a further 6 hours. After cooling in ice-water the mixture was treated with water (20 mL) dropwise with stirring over 10 minutes. The mixture was again allowed to warm to room temperature and stirred for 2 hours before evaporating the bulk of the solvent. The residue was then cooled in ice-water and 50% NaOH (aq.) (20 mL) added dropwise with stirring. The resulting mixture was stirred and heated at 90° C. for 4 hours then cooled to room temperature and extracted three times with Et2O. The combined extracts were washed with water followed by brine, dried over MgSO4 and evaporated to dryness. The crude product was then purified by flash silica chromatography (eluent 0-10% 7N ammonia in MeOH/DCM) and pure fractions evaporated to afford 4-amino-4-(4-chlorophenyl)butan-1-ol (3.88 g, 73.0%) as a colourless, transparent gum.

1. temperaturethen heated
2. temperatureat reflux for a further 6 hours
3. stirringwith stirring over 10 minutes
4. temperatureto warm to room temperature
5. stirringstirred for 2 hours
6. custombefore evaporating the bulk of the solvent
7. temperatureThe residue was then cooled in ice-water
8. addition50% NaOH (aq.) (20 mL) added dropwise
9. stirringwith stirring
10. stirringThe resulting mixture was stirred
11. temperatureheated at 90° C. for 4 hours
12. temperaturethen cooled to room temperature
13. extractionextracted three times with Et2O
14. washThe combined extracts were washed with water
15. dry with materialdried over MgSO4
16. customevaporated to dryness
17. customThe crude product was then purified by flash silica chromatography (eluent 0-10% 7N ammonia in MeOH/DCM) and pure fractions
18. customevaporated