tert-Butanol → HCID 59497230, compound

HRID 1747481Notes

Reaction equation

HRID 1747481 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][N:8]2[CH3:11])=[C:4]([CH2:12][N:13]2[C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=3[N:15]([CH:22]([CH2:27][CH2:28][CH3:29])[CH2:23][C:24]([OH:26])=[O:25])[C:14]2=[O:30])[CH:3]=1.CC([OH:35])(C)C.C1C(=O)N(Br)C(=O)C1>C1COCC1.[Zn]>[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][C:7](=[O:35])[N:8]2[CH3:11])=[C:4]([CH2:12][N:13]2[C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=3[N:15]([CH:22]([CH2:27][CH2:28][CH3:29])[CH2:23][C:24]([OH:26])=[O:25])[C:14]2=[O:30])[CH:3]=1

Participants

6

Reactant 3

HCID 6386tert-ButanolHCID 67184N-bromobutanimideHCID 59497272HCID 59497272, compound

Product 1

HCID 59497230HCID 59497230, compoundYield 25%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 3-[3-(6-bromo-1-methyl-1H-indol-4-ylmethyl)-2-oxo-2,3-dihydro-benzimidazol-1-yl]-hexanoic acid (71 mg, 0.15 mmol) in THF (11 mL) was added t-BuOH (1 mL). A solution of NBS (58 mg, 0.32 mmol) in THF (0.5 mL) was added and the resulting mixture was stirred at ambient temperature for 15 m, concentrated and used directly. This crude intermediate was dissolved in acetic acid (1.5 mL). Zn powder (70 mg, 1.1 mmol) was added and the resulting mixture was agitated for 15 m. The reaction mixture was filtered and the mother liquors were concentrated and purified directly by preparative HPLC using an acetonitrile/water/formic acid gradient to provide 12 mg (25%) of the title compound. LCMS (ESMS): m/z 486.88 (M+H).

Workup

  1. concentrationconcentrated
  2. dissolutionThis crude intermediate was dissolved in acetic acid (1.5 mL)
  3. stirringthe resulting mixture was agitated for 15 m
  4. filtrationThe reaction mixture was filtered
  5. concentrationthe mother liquors were concentrated
  6. custompurified directly by preparative HPLC

Sources & evidence

ORD record
ord-54dbcb554a8f49fa8ac001280a1e7b6e
Source dataset
uspto-grants-2015_10
Patent number
US09150556B2

Reaction notes

Loading…