Hydrochloric Acid → HCID 13494759, compound

A 1 M solution of phenylmagnesium bromide (49.0 g, 0.27 mol) in THF was added dropwise to (S)-isoleucine methyl ester hydrochloride (9.8 g, 54.0 mmol) at 0° C. and then stirred for 17 h at room temperature. The reaction mixture was cooled to 0° C., quenched with dropwise addition of saturated NH4Cl and then diluted with AcOEt and water until partition occurred. Organic products were extracted into AcOEt (3×50 ml), dried over MgSO4/K2CO3 and concentrated to obtain a crude product. The crude product was dissolved in diethyl ether (150 ml), treated with concentrated HCl until all of the amine was converted to its HCl salt. The amine-HCl salt was stirred overnight, diluted with water until partition occured. The non-basic organics were extracted into diethyl ether (5×100 ml) and then the aqueous layer was made basic with NaOH pellets. After stirring for 4 h, organic products were extracted into AcOEt (4×75 ml) and dried over MgSO4/K2CO3. Concentration gave a crude product (6.1 g, 42%) as a pale yellow solid. This contaminated with the amino ester derived from the starting material, however was used for the next step without further purification. A small amount of the crude product (1.1 g) was purified over silica gel by means of dry-flash column chromatography, eluting first with CH2Cl2, then with a mixture of AcOEt and petrol, increasing from 40% up to 80%. From this, a pure amino alcohol 13 (654 mg, 60%) was obtained as a white amorphous solid. m.p. 128–129° C. (lit 135–136° C.). [α]D25=−128.17° (c, 4.26 in CHCl3) (lit: −124.1° (c, 1.23 in CHCl3)). δH 0.72 (3H, t, J=7.2 Hz, CH3), 0.94 (3H, d, J=6.9 Hz, CH3), 0.80–1.10 (1H, m, CH2), 1.40–1.60 (1H, m, CH), 1.76–1.94 (1H, m, CH2), 0.60–2.10 (3H, OH and NH2), 3.85 (1H, d, J=1.5 Hz, CH—NH2), 7.10–7.70 (10H, m, Ar—H). δC 12.1 (CH3—CH2), 18.7 (CH3—CH), 22.5 (CH2), 34.8 (CH—Me), 60.9 (CH—NH2), 79.6 (C), 125.5, 125.9, 126.1, 126.5, 127.8, 128.2, 144.9, 147.9 (Ar). νmax (cm−1): 3343, 3279 (N—H and O—H), 3085, 3023 (Ar C—H), 2959, 2926, 2873 (methyl and methylene C—H), 1589, 1491, 1447 (Ar C═C). m/e 270 (MH+, 4%), 252 (20%), 86 (100%).

1. temperatureThe reaction mixture was cooled to 0° C.
2. customquenched with dropwise addition of saturated NH4Cl
3. additiondiluted with AcOEt and water
4. customuntil partition
5. extractionOrganic products were extracted into AcOEt (3×50 ml)
6. dry with materialdried over MgSO4/K2CO3
7. concentrationconcentrated
8. customto obtain a crude product
9. customuntil partition
10. extractionThe non-basic organics were extracted into diethyl ether (5×100 ml)
11. stirringAfter stirring for 4 h
12. extractionorganic products were extracted into AcOEt (4×75 ml)
13. dry with materialdried over MgSO4/K2CO3
14. concentrationConcentration
15. customgave a crude product (6.1 g, 42%) as a pale yellow solid
16. customhowever was used for the next step without further purification
17. customA small amount of the crude product (1.1 g) was purified over silica gel by means of dry-flash column chromatography
18. washeluting first with CH2Cl2
19. additionwith a mixture of AcOEt and petrol
20. temperatureincreasing from 40% up to 80%

ORD record

ord-b3ec575d49624c7db5e3d86d4f8f4185

Source dataset

uspto-grants-2006_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07126028B1