2-Chloro-5-fluorobenzeneboronic acid → Tert-butyl n-(3-{5-[2'-chloro-5'-fluoro-2-(methoxymethyl)biphenyl-4-yl]-1,2,4-oxadiazol-3-yl}benzyl)-n-methylglycinate

HRID 2410591Notes

Reaction equation

HRID 2410591 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][N:11]=[C:10]([C:13]3[CH:14]=[C:15]([CH:27]=[CH:28][CH:29]=3)[CH2:16][N:17]([CH3:26])[CH2:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[N:9]=2)=[CH:4][C:3]=1[CH2:30][O:31][CH3:32].[Cl:33][C:34]1[CH:39]=[CH:38][C:37]([F:40])=[CH:36][C:35]=1B(O)O>>[Cl:33][C:34]1[CH:39]=[CH:38][C:37]([F:40])=[CH:36][C:35]=1[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][N:11]=[C:10]([C:13]3[CH:14]=[C:15]([CH:27]=[CH:28][CH:29]=3)[CH2:16][N:17]([CH3:26])[CH2:18][C:19]([O:21][C:22]([CH3:25])([CH3:23])[CH3:24])=[O:20])[N:9]=2)=[CH:4][C:3]=1[CH2:30][O:31][CH3:32].[ClH:33].[Cl:33][C:34]1[CH:39]=[CH:38][C:37]([F:40])=[CH:36][C:35]=1[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][N:11]=[C:10]([C:13]3[CH:14]=[C:15]([CH:27]=[CH:28][CH:29]=3)[CH2:16][N:17]([CH3:26])[CH2:18][C:19]([OH:21])=[O:20])[N:9]=2)=[CH:4][C:3]=1[CH2:30][O:31][CH3:32]

Participants

4

Reactant 2

HCID 226481162-Chloro-5-fluorobenzeneboronic acidHCID 58066337HCID 58066337, compound

Product 2

HCID 66677949Tert-butyl n-(3-{5-[2'-chloro-5'-fluoro-2-(methoxymethyl)biphenyl-4-yl]-1,2,4-oxadiazol-3-yl}benzyl)-n-methylglycinateHCID 131731801HCID 131731801, compound

Procedure

Tert-butyl N-(3-{5-[2′-chloro-5′-fluoro-2-(methoxymethyl)biphenyl-4-yl]-1,2,4-oxadiazol-3-yl}benzyl)-N-methylglycinate was prepared following the general procedure 11 starting from Intermediate 41 and 2-chloro-5-fluorophenylboronic acid (Combiblocks BB-2251). After purification by flash chromatography (silica, cHex/EtOAc), the ester derivative was deprotected following the general procedure 8. After purification by precipitation from ACN, the title compound was obtained as a white powder. HPLC (Method A), Rt 4 min (purity: 97.1%). LC/MS (Method B): 494.1 (M−H)−, 495.9 (M+H)+. Elemental analysis: [C26H23N3O4ClF—HCl-0.25H20] Corrected: C, 58.16%; H, 4.60%; N, 7.83%; Cl, 13.21%. Found: C, 58.18%; H, 4.61%; N, 7.77%; Cl, 13.23%. 1H NMR (DMSO-d6, 300 MHz) δ 8.35 (m, 2H), 8.22 (m, 2H), 7.81 (d, J=7.8 Hz, 1H), 7.75-7.67 (m, 2H), 7.52 (d, J=8.0 Hz, 1H), 7.43-7.33 (m, 2H), 4.50 (s, 2H), 4.32 (d, J=13.1 Hz, 1H), 4.27 (d, J=13.1 Hz, 1H), 4.11 (s, 2H), 3.27 (s, 3H), 2.81 (s, 3H).

Workup

  1. customAfter purification by flash chromatography (silica, cHex/EtOAc)
  2. customAfter purification
  3. customby precipitation from ACN

Sources & evidence

ORD record
ord-bb9f2a9abfc14a95b52772560fc22b72
Source dataset
uspto-grants-2014_08
Patent number
US08815919B2

Reaction notes

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