Sodium Hydroxide → HCID 86635140, compound

Temperature

100 °C

To a solution consisting of (R)-(−)-2-amino-1-phenylethanol (4.80 g, 35.0 mmol) in and 1,4-dioxane (150 mL) at rt was added dropwise a solution consisting of 4,6-dichloropyrimidine (5.21 g, 35.0 mmol) and 1,4-dioxane (75 mL). Upon complete addition, NaHCO3 (17.6 g, 0.210 mol) was added and the mixture was heated to reflux (100° C.) for 17 h. The reaction mixture was cooled, diluted with water (60 mL) and the pH was adjusted to 12 by the addition of a 1 N NaOH (25 mL). The solution was extracted with CH2Cl2 (75 mL), washed with satd. aq. NaCl (50 mL), and the organic extract was dried (Na2SO4) and concentrated. The crude material (8.2 g) was suspended in CH2Cl2 (40 mL) and warmed to 50° C. to give a homogeneous solution. The solution was cooled to rt and treated with a few drops of hexanes to give the title compound as a pale yellow solid (7.0 g, 81%). MS (ESI): mass calcd. for C21H20F3N3O2, 403.2; m/z found, 404.2 [M+H]+. 1H NMR (CD3OD): 8.44 (s, 1H), 8.15 (s, 1H), 8.09 (dd, J=8.8, 2.2 Hz, 1H), 7.43 (d, J=7.7 Hz, 2H), 7.34 (t, J=7.7 Hz, 2H), 7.27-7.25 (m, 2H), 6.86 (s, 1H), 4.91-4.88 (m, 1H), 4.21 (q, J=7.1 Hz, 2H), 3.76-3.68 (m, 1H), 3.58 (dd, J=13.7, 7.7 Hz, 1H), 1.45 (t, J=7.1 Hz, 3H).

1. customat rt
2. additionwas added dropwise a solution
3. additionwas added
4. temperaturethe mixture was heated
5. temperatureThe reaction mixture was cooled
6. extractionThe solution was extracted with CH2Cl2 (75 mL)
7. washwashed with satd
8. extractionaq. NaCl (50 mL), and the organic extract
9. dry with materialwas dried (Na2SO4)
10. concentrationconcentrated
11. temperaturewarmed to 50° C.
12. customto give a homogeneous solution
13. temperatureThe solution was cooled to rt

ORD record

ord-6520969383b0490493efbbbb49fd02a1

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08598202B2