Aluminium lithium hydride → 7-fluoro-3,4-dihydro-1,5-benzothiazepin-5(2H)-amine

Temperature

0 °C

7-fluoro-5-nitroso-2,3,4,5-tetrahydro-1,5-benzothiazepine (449 mg, 2.11 mmol) was suspended in THF (1 mL of freshly distilled) and cooled to 0° C. in an ice bath. Lithium aluminum hydride (80 mg, 2.11 mmol) was added in a portion-wise fashion. The flask was removed from the ice bath and allowed to warm to room temperature and was stirred for 2 hours. Water (0.08 mL) was added and stirred for 10 minutes. 15% sodium hydroxide (0.08 mL) was added stirred for 10 minutes. Water (0.024 mL) was added and stirred for 10 minutes. The reaction was extracted with dichloromethane (2×25 mL). The organics were concentrated to a residue, then taken up in minimal amount of dichloromethane and then hydrogen chloride in ether (1 M) was added until precipatation formed, the precipatate was filtered off to give 7-fluoro-3,4-dihydro-1,5-benzothiazepin-5(2H)-amine (471 mg, 95%). 1H NMR (CD-3OD, 300 MHz): δ 7.59 (t, 1H, J=7.5 Hz), 7.28 (d, 1H, J=9.9 Hz), 7.00 (t, 1H, J=8.2 Hz), 3.52 (t, 1H, J=7.5 Hz), 2.92–2.86 (m, 1H), 2.72–2.70 (m, 2H), 2.40–2.31 (m, 1H), 2.2–2.18 (m, 2H) ppm.

1. distillationof freshly distilled) and
2. customThe flask was removed from the ice bath
3. temperatureto warm to room temperature
4. additionWater (0.08 mL) was added
5. stirringstirred for 10 minutes
6. addition15% sodium hydroxide (0.08 mL) was added
7. stirringstirred for 10 minutes
8. additionWater (0.024 mL) was added
9. stirringstirred for 10 minutes
10. extractionThe reaction was extracted with dichloromethane (2×25 mL)
11. concentrationThe organics were concentrated to a residue
12. additionhydrogen chloride in ether (1 M) was added until precipatation
13. customformed
14. filtrationthe precipatate was filtered off

ORD record

ord-4e843f65c8ef4057bfad5f051d6bccd1

Source dataset

uspto-grants-2006_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07071186B2