Cesium carbonate → Ethyl 2-(3-(benzo[c][1,2,5]oxadiazol-5-yl)-5-chloro-4-(cyclopropylmethoxy)phenyl)-4-methylpentanoate

HRID 385477Notes

Reaction equation

HRID 385477 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:14]([CH2:20][CH:21]([CH3:23])[CH3:22])[C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH:5]=[C:6]([Cl:13])[C:7]=1[O:8][CH2:9][CH:10]1[CH2:12][CH2:11]1.C([O-])([O-])=O.[Cs+].[Cs+].CC1(C)C(C)(C)OB([C:38]2[CH:46]=[CH:45][C:41]3=[N:42][O:43][N:44]=[C:40]3[CH:39]=2)O1>CN(C=O)C.O>[N:42]1[O:43][N:44]=[C:40]2[CH:39]=[C:38]([C:2]3[CH:3]=[C:4]([CH:14]([CH2:20][CH:21]([CH3:23])[CH3:22])[C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH:5]=[C:6]([Cl:13])[C:7]=3[O:8][CH2:9][CH:10]3[CH2:12][CH2:11]3)[CH:46]=[CH:45][C:41]=12

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 467380042,1,3-Benzoxadiazole-5-boronic acid, pinacol esterHCID 68732072Ethyl 2-(3-bromo-5-chloro-4-(cyclopropylmethoxy)phenyl)-4-methylpentanoate

Product 1

HCID 57995660Ethyl 2-(3-(benzo[c][1,2,5]oxadiazol-5-yl)-5-chloro-4-(cyclopropylmethoxy)phenyl)-4-methylpentanoateYield 45.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of ethyl 2-(3-bromo-5-chloro-4-(cyclopropylmethoxy)phenyl)-4-methylpentanoate (0.5 g, 1.240 mmol) in a mixture of DMF (20 mL) and water (5 mL) were added Cs2CO3 (1.4 g, 4.342 mmol), Pd(TPP)4 (286 mg, 2.480 mmol) and 5-(4,4,5,5,-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[c][1,2,5]oxadiazole (355 mg, 1.364 mmol) at RT under N2 atmosphere and the resulting mixture was stirred at 80° C. for 14 h. After completion of starting material (by TLC), the solids were removed via filtration through a bed of Celite™ was washing with EtOAc (3×100 mL). The combined organic layers were washed with water (3×50 mL), brine and dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by column chromatography to afford ethyl 2-(3-(benzo[c][1,2,5]oxadiazol-5-yl)-5-chloro-4-(cyclopropylmethoxy)phenyl)-4-methylpentanoate (250 mg) as an off white solid.

Workup

  1. customAfter completion of starting material (by TLC), the solids were removed via filtration through a bed of Celite™
  2. washwas washing with EtOAc (3×100 mL)
  3. washThe combined organic layers were washed with water (3×50 mL), brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude material was purified by column chromatography

Sources & evidence

ORD record
ord-cff6f6d9e6484705984fd70a735cde99
Source dataset
uspto-grants-2013_02
Patent number
US08367863B2

Reaction notes

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