Methanol → 3-(1-(4-bromobenzyl)-5-(quinolin-2-ylmethoxy)-1H-benzo[d]imidazol-2-yl)-2,2-dimethylpropanoic acid

HRID 2178429Notes

Reaction equation

HRID 2178429 reaction equation
[Li+].[OH-].[Br:3][C:4]1[CH:40]=[CH:39][C:7]([CH2:8][N:9]2[C:13]3[CH:14]=[CH:15][C:16]([O:18][CH2:19][C:20]4[CH:29]=[CH:28][C:27]5[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=5)[N:21]=4)=[CH:17][C:12]=3[N:11]=[C:10]2[CH2:30][C:31]([CH3:38])([CH3:37])[C:32]([O:34]CC)=[O:33])=[CH:6][CH:5]=1.C1COCC1.CO>O>[Br:3][C:4]1[CH:5]=[CH:6][C:7]([CH2:8][N:9]2[C:13]3[CH:14]=[CH:15][C:16]([O:18][CH2:19][C:20]4[CH:29]=[CH:28][C:27]5[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=5)[N:21]=4)=[CH:17][C:12]=3[N:11]=[C:10]2[CH2:30][C:31]([CH3:37])([CH3:38])[C:32]([OH:34])=[O:33])=[CH:39][CH:40]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 90415263ethyl 3-(1-(4-bromobenzyl)-5-(quinolin-2-ylmethoxy)-1H-benzo[d]imidazol-2-yl)-2,2-dimethylpropanoate

Product 1

HCID 862813933-(1-(4-bromobenzyl)-5-(quinolin-2-ylmethoxy)-1H-benzo[d]imidazol-2-yl)-2,2-dimethylpropanoic acidYield 83%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
80 °C

Procedure

A solution of LiOH (39 mg, 0.9 mmol) in water (2 mL) was added to a 20 mL round-bottomed flask containing ethyl 3-(1-(4-bromobenzyl)-5-(quinolin-2-ylmethoxy)-1H-benzo[d]imidazol-2-yl)-2,2-dimethylpropanoate (106 mg, 0.19 mmol), THF (3 mL), MeOH (3 mL), and water (3 mL). The resulting solution was heated to 80° C. After 2 h, the solution was concentrated to dryness and the residue was treated with sat. ammonium chloride (20 mL) and EtOAc (20 mL). The organic layer was separated and the aqueous layer was further extracted with EtOAc (2×20 mL). The combined organic layers were dried with sodium sulfate, filtered, and concentrated to dryness. The residue was subjected to FCC to give the title compound (84 mg, 83%). MS (ESI): mass calcd. for C29H26BrN3O3, 543.12; m/z found, 544.2 [M+H]+. 1H NMR (500 MHz, CD3OD) δ 9.00 (d, J=8.7, 1H), 8.32 (d, J=8.5, 1H), 8.26 (d, J=8.4, 1H), 8.15-8.08 (m, 2H), 7.94-7.88 (m, 1H), 7.59 (d, J=8.8, 1H), 7.57-7.51 (m, 3H), 7.41 (dd, J=9.1, 2.4, 1H), 7.19 (d, J=8.6, 2H), 5.82 (s, 2H), 5.76 (s, 2H), 3.53 (s, 2H), 1.42 (s, 6H).

Workup

  1. concentrationthe solution was concentrated to dryness
  2. additionthe residue was treated with sat. ammonium chloride (20 mL) and EtOAc (20 mL)
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was further extracted with EtOAc (2×20 mL)
  5. dry with materialThe combined organic layers were dried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-bcb5c366ae8547909697fa0c6d24a835
Source dataset
uspto-grants-2015_06
Patent number
US09067917B2

Reaction notes

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