Water → 3-Methyl-N1-(2,2,2-trifluoroethyl)-1,3-butanediamine

Temperature

70 °C

3-Azido-3-methyl-N-(2,2,2-trifluoroethyl)butanamide (10.9 g, 48.4 mmol) was dissolved into anhydrous THF (50 mL) and added dropwise to a suspension of LAH (3.67 g, 2.0 equiv, 96.8 mmol) in anhydrous THF (200 mL) to maintain the reaction at reflux (30 min). After complete addition, the flask was fitted with a condenser and the reaction heated in a 70° C. oil bath for 8 h. The reaction mixture was cooled in an ice bath and water (4 mL) was added dropwise over 20 min. Then 15% NaOH solution (4 mL) was added dropwise over 10 min. The suspension was stirred for a further 10 min and water (4 mL) was added in one portion and the mixture stirred for 30 min to a give fine white suspension. The suspension was filtered through a pad of Celite® and washed with isopropyl alcohol (2×200 mL). Aqueous acid (6 N HCl, 10.0 mL) was added to the combined filtrate and concentrated on a rotovap to an oily residue. The residue was partitioned between DCM (100 mL) and water (100 mL). The aqueous layer was adjusted to pH ˜14 and the organic layer was separated and the aqueous phase was extracted with DCM (2×50 mL). The combined organic layers were combined and dried over anhydrous MgSO4, filtered and concentrated with a bath temperature between 10-13° C. to an orange liquid (8.84 g, quant). 1H NMR (CDCl3, 400 MHz): δ 1.15 (s, 6H), 1.55-1.62 (t, J=7.2, 2H), 2.81-2.86 (t, J=7.2, 2H) 3.15-3.22 (q, J=9.6, 2H). LRMS (ESI+) for C7H15F3N2 (184.1); Found: 185 (MH+).

1. temperatureto maintain
2. customthe reaction
3. temperatureat reflux (30 min)
4. additionAfter complete addition
5. customthe flask was fitted with a condenser
6. temperatureThe reaction mixture was cooled in an ice bath
7. stirringthe mixture stirred for 30 min to a give fine white suspension
8. filtrationThe suspension was filtered through a pad of Celite®
9. washwashed with isopropyl alcohol (2×200 mL)
10. additionAqueous acid (6 N HCl, 10.0 mL) was added to the combined filtrate
11. concentrationconcentrated on a rotovap to an oily residue
12. customThe residue was partitioned between DCM (100 mL) and water (100 mL)
13. customthe organic layer was separated
14. extractionthe aqueous phase was extracted with DCM (2×50 mL)
15. dry with materialdried over anhydrous MgSO4
16. filtrationfiltered
17. concentrationconcentrated with a bath temperature between 10-13° C. to an orange liquid (8.84 g, quant)

ORD record

ord-c6225b1935ac44e9a9059c7d4a823a90

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08278482B2