Reference

Process for preparation of Nebivolol from 6-fluoro-3,4-dihydro-a-[[(phenylmethyl)amino]methyl]-2H-1-benzopyran- 2-methanol and 6-fluoro-3,4-dihydro-2-oxiranyl-2H-benzopyran

Process for preparation of Nebivolol from 6-fluoro-3,4-dihydro-a-[[(phenylmethyl)amino]methyl]-2H-1-benzopyran- 2-methanol and 6-fluoro-3,4-dihydro-2-oxiranyl-2H-benzopyran.Some commonly used reagents like 152520-56-4 is used in this experiment. Sheth, Rakesh; Attanti, Srinivasarao Veeravenkata; Patel, Hasmukh Mathurbhai; Gupta, Vinodkumar; Nadkarni, Sunil Sadanand (Torrent Pharmaceuticals Limited, India). PCT Int. Appl. WO 2006025070 A2 9 Mar 2006, 72 pp. DESIGNATED STATES: W: AE, AG, AL, AM, AT, AU, AZ, BA, BB, BG, BR, BW, BY, BZ, CA, CH, CN, CO, CR, CU, CZ, DE, DK, DM, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, MA, MD, MG, MK, MN, MW, MX, MZ, NA, NG, NI, NO, NZ, OM, PG, PH, PL, PT, RO, RU, SC, SD, SE, SG, SK, SL, SM, SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, YU, ZA, ZM, ZW; RW: AT, BE, BF, BJ, CF, CG, CH, CI, CM, CY, DE, DK, ES, FI, FR, GA, GB, GR, IE, IS, IT, LU, MC, ML, MR, NE, NL, PT, SE, SN, TD, TG, TR. (English). (World Intellectual Property Organization). CODEN: PIXXD2. APPLICATION: WO 2005-IN252 1 Aug 2005. PRIORITY: IN 2004-MU811 30 Jul 2004. DOCUMENT TYPE: Patent CA Section: 27 (Heterocyclic Compounds (One Hetero Atom)) Section cross-reference(s): 63 A process for prepn of Nebivolol or its hydrochloride comprises reaction of 6-fluoro-3,4-dihydro-a-[[(phenylmethyl)amino]methyl]-2H-1-benzopyran- 2-methanol (I) with 6-fluoro-3,4-dihydro-2-oxiranyl-2H-benzopyran (II) in an org. solvent and isolation at -5° to -25° to give N-benzylnebivolol followed by debenzylation using Pd/C and optional conversion to the hydrochloride. Thus, I (prepn. given) and II (prepn. given) were heated together in MeOH at 65-70° for 15 h followed by cooling to -10° to -15° to give N-benzylnebivolol, which was hydrogenated in 2-methoxyethanol over Pd/C to give Nebivolol base. The latter was stirred with HCl in MeOH for 4 h at 28-32° to give nebivolol hydrochloride. .