Benzaldehyde → tert-butyl N-[2-(benzylamino)ethyl]-3-methyl-L-valinate

Temperature

50 °C

A solution of benzaldehyde (23 g, 217 mmol) and the product of Example 111-3 (50 g, 217 mmol, 1 equivalent) in 50:50 mixture of toluene and methanol (total volume=1400 mL), stirred at 50° C. overnight, cooled to −3° C., treated with NaBH4 (16.6 g, 434 mmol, 2equivalents) slowly over 5 hours, and stirred at room temperature for 16 hours. The reaction mixture was quenched with a saturated NaHCO3 solution (1400 mL) and extracted with ethyl acetate (1.3 L). The layers were separated and the aqueous layer was extracted with ethyl acetate (850 mL). The organic layers were combined, washed with brine (900 mL), and concentrated. The residue was dissolved in heptanes (700 mL), decanted inorganic salt, distilled to oil and chased to yield 69.4 g of crude material. 1H NMR (CDCl3): δ 7.05-7.3(m, 7H), 3.75(d, 2H), 2.4-2.8(m, 5H), 1.4(s, 9H), 0.87(s, 9H).

1. temperaturecooled to −3° C.
2. stirringstirred at room temperature for 16 hours
3. customThe reaction mixture was quenched with a saturated NaHCO3 solution (1400 mL)
4. extractionextracted with ethyl acetate (1.3 L)
5. customThe layers were separated
6. extractionthe aqueous layer was extracted with ethyl acetate (850 mL)
7. washwashed with brine (900 mL)
8. concentrationconcentrated
9. dissolutionThe residue was dissolved in heptanes (700 mL)
10. customdecanted inorganic salt
11. distillationdistilled to oil

ORD record

ord-ac5473404a2041a18baa4aa6a6d30842

Source dataset

uspto-grants-2010_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07834043B2