Benzylamine → HCID 67142322, compound

Temperature

6 °C

In a 4 L flask with overhead stirrer, thermometer, dropping funnel and under nitrogen were combined 150 g boc-(D)-serine (0.731 mol) (ee>99%), 1.5 kg ethyl acetate and 221.5 g 4-methylmorpholine (2.19 mol). The reactor was cooled in an ice bath to 4-8° C. and 129.4 g benzylamine (1.24 mol) slowly added. After complete addition a thick slurry was obtained. 525 g of T3P® in ethyl acetate (2,4,6-tri-n-propyl-2,4,6-trioxo-1,3,5,2,4,6-trioxatriphosphorinane as a 50% w/w solution in ethyl acetate, 0.826 mol) were slowly added, maintaining the temperature below 15° C. The mixture was cooled and stirred on ice at 4-8° C. for 1.5 hours, then at 25° C. for 2 hours. The reaction was quenched by the addition of 400 ml water and stirred for a further 30 minutes. The phases were separated and the aqueous phase re-extracted with 750 ml ethyl acetate. The combined organic phases were washed 200 ml water, adjusted to pH 6 with 37% HCl, then washed a second time with 150 ml water. The ethyl acetate was stripped and exchanged to toluene. The product was crystallised from 1 kg toluene by cooling to 4-8° C. The product was filtered and washed with 2×100 ml toluene. After drying under vacuum at 40° C., 153.8 g (yield 71.5%) (R)-boc-2-amino-N-benzyl-3-hydroxy-propionamide (III) were obtained. HPLC purity >99% , ee 99%, 1H NMR (400 MHz, CDCl3): δ=1.42 (s, 9 H), 3.12 (br, 1 H), 3.65-3.69 (m, 1 H), 4.12-4.18 (m, 2 H), 4.36-4.53 (m, 2 H), 5.62 (d, J=6.0, 1 H), 7.08 (br, 1 H), 7.21-7.36 (m, 5 H).

1. customIn a 4 L flask with overhead stirrer, thermometer, dropping
2. customfunnel and under nitrogen were combined
3. additionAfter complete addition a thick slurry
4. customwas obtained
5. temperaturemaintaining the temperature below 15° C
6. temperatureThe mixture was cooled
7. waitat 25° C. for 2 hours
8. customThe reaction was quenched by the addition of 400 ml water
9. stirringstirred for a further 30 minutes
10. customThe phases were separated
11. extractionthe aqueous phase re-extracted with 750 ml ethyl acetate
12. washThe combined organic phases were washed 200 ml water
13. washwashed a second time with 150 ml water
14. customThe product was crystallised from 1 kg toluene
15. temperatureby cooling to 4-8° C
16. filtrationThe product was filtered
17. washwashed with 2×100 ml toluene
18. customAfter drying under vacuum at 40° C.

ORD record

ord-71689fed4e534bbd9940d787de3ad9e5

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08598386B2