2-BOC-6-FLUORO-3,4-DIHYDRO-1H-ISOQUINOLINE-1-CARBOXYLIC ACID synthesis

Yield:-

Reaction Conditions:

with water;sodium hydroxide in tert-butyl alcohol; for 18 h;

Steps:

6.1 Example 6 6-Fluoro-2-[(S)-3-methyl-2-((S)-2-methylamino-propionylamino)-butyryl]-l, 2,3,4- tetrahydro-isoquinoline-l-carboxylic acid (2,6-difluoro-phenyl)-amide Step 1 :

In a 50 niL round-bottomed flask, 6-fluoro- 1,2,3 ,4-tetrahydroisoquinoline-l- carboxylic acid hydrochloride (500 mg, 2.16 mmol, Eq: 1.00) and 2 N NaOH (3.24 mL, 6.48 mmol, Eq: 3) were combined with t-BuOH (3.00 mL) to give a light brown solution and BOC-anhydride (565 mg, 601 μ, 2.59 mmol, Eq: 1.2) was added. After stirring 18 h, the reaction was diluted with water and extracted ether. The aqueous layer was acidified with saturated KHS0₄ and extracted with EtOAc. The combined organic extracts were washed with brine, dried over Na₂S0₄, filtered and concentrated to give 0.6448g 6-fluoro- 3,4-dihydro-lH-isoquinoline-l ,2-dicarboxylic acid 2-tert-butyl ester as white foam which was used without purification. 100 % MS m/z 193.9 (M-BOC)

References:

WO2014/26882,2014,A1 Location in patent:Page/Page column 39-40