HCID 86663634, compound → Valbenazine

Participants

Reaction Steps

1 (200 mg, 0.63 mmol) was dissolved in 3 mL anhydrous CH2Cl2 and DMAP (75.0 mg, 0.63 mmol) and Cbz-L-valine (190 mg, 0.75 mmol) were added and the mixture stirred for 5 min. DCC (155 mg, 0.75 mmol) was added and a white precipitate formed immediately. The mixture was stirred overnight then filtered and concentrated. Purification via flash column chromatography (0.2:9.8, MeOH:CH2Cl2) gave 360 mg (0.63 mmol) of 2-benzyloxycarbonylamino-3-methyl-butyric acid (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-yl ester 2a as a pale yellow solid in quantitative yield. Compound 2a (163 mg, 0.29 mmol) was dissolved in MeOH (10 mL) and Pd/C was added and the mixture was purged with H2. The mixture was stirred overnight, filtered through celite and concentrated. Purification via flash column chromatography (0.5:9.5, MeOH:CH2Cl2) gave 105 mg (0.25 mmol) of (S)-2-amino-3-methyl-butyric acid (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-yl ester 2-1 in 85% yield. MS calcd: (419). Found 419.3 (M+H).

Provenance & Evidence