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4-Bromo-6,7-dihydroisoquinolin-8(5H)-one (4.81 g, 21.3 mmol), titanium (IV) isopropoxide (12.5 mL, 42.6 mmol) and ammonia, 2.0 M solution in MeOH (53.2 mL, 106 mmol) were stirred at RT for 5 h. The reaction was cooled to 0° C. and NaBH4 (1.21 g, 31.9 mmol) was added portionwise over 10 min; the resulting mixture was stirred at RT for an additional 2 h. The reaction was quenched by pouring it into aq. ammonium hydroxide (25%), the precipitate was filtered and washed with EtOAc (3×, each time suspended in AcOEt and stirred for 5 min). The organic layer was separated and the remaining aqueous layer was extracted with EtOAc. The combined organic extracts were extracted with 1 M HCl. The acidic aqueous extracts were washed with ethyl acetate (1×), then treated with aqueous sodium hydroxide (2 M) to give pH 10-12, and extracted with EtOAc (3×). The combined second organic extracts were washed with brine, dried (Na2SO4), and concentrated in vacuo to afford the title compound (4.11 g, 85%) as brown solid. MS: 225 (M+, 1 Br).

1. customThe reaction was quenched
2. additionby pouring it into aq. ammonium hydroxide (25%)
3. filtrationthe precipitate was filtered
4. washwashed with EtOAc (3×
5. stirringstirred for 5 min)
6. customThe organic layer was separated
7. extractionthe remaining aqueous layer was extracted with EtOAc
8. extractionThe combined organic extracts were extracted with 1 M HCl
9. washThe acidic aqueous extracts were washed with ethyl acetate (1×)
10. additiontreated with aqueous sodium hydroxide (2 M)
11. customto give pH 10-12
12. extractionextracted with EtOAc (3×)
13. washThe combined second organic extracts were washed with brine
14. dry with materialdried (Na2SO4)
15. concentrationconcentrated in vacuo