Hydrochloric Acid → 2(S)-[2,2-difluoro-1(S)-(4-fluorophenyl)-2-pyridin-2-ylethylamino]-4,4-dimethylpentanoic acid

To a solution of [2,2-difluoro-1(S)-(4-fluorophenyl)-2-pyridin-2-ylethyl]-[3,3-dimethyl-1(S)-(4-methyl-2,6,7-trioxa-bicyclo[2.2.2]oct-1-yl)butyl]amine (265 mg, 0.571 mmol) in a mixture of THF (5 ml) and water (5 ml) was added 1N HCl (2 ml, 2 mmol) and the reaction mixture was stirred at room temperature for 2 h. 1N NaOH (3.6 ml, 3.6 mmol) was added and stirring was continued at room temperature for 4 h. The solvent was evaporated using rotavap and 6N HCl was added dropwise to adjust the pH to 6. The precipitates were filtered and dried to obtain 2(S)-[2,2-difluoro-1(S)-(4-fluorophenyl)-2-pyridin-2-ylethylamino]-4,4-dimethylpentanoic acid (100 mg) as a white solid which was converted to the title compound as described in Example 1, Step 12 above. LC/MS: 443.2 (M−1)−1, 445.4 (M+1)+1, 466.9 (M+Na). 1HNMR (DMSO-d6): δ 8.7 (d, 1H), 8.6 (s, 1H), 7.95 (t, 1H), 7.6 (d, 1H), 7.55 (t, 1H), 7.4 (d, 2H), 7.2 (d, 2H), 4.6 (m, 1H), 2.6 (t, 1H), 1.3 (m, 4H), 0.6 (S, 10H), 0.25 (t, 1H).

1. stirringstirring
2. waitwas continued at room temperature for 4 h
3. customThe solvent was evaporated
4. addition6N HCl was added dropwise
5. filtrationThe precipitates were filtered
6. customdried

ORD record

ord-cc3027fa4b24423b9d8fe525dbf0a4c2

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08013186B2