2-(2-Bromoethoxy)tetrahydro-2H-pyran → tert-Butyl 4-(4-bromo-1-(2-hydroxyethyl)-1H-imidazol-2-yl)piperidine-1-carboxylate

HRID 2283935Notes

Reaction equation

HRID 2283935 reaction equation
[Br:1][C:2]1[N:3]=[C:4]([CH:7]2[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]2)[NH:5][CH:6]=1.Br[CH2:21][CH2:22][O:23]C1CCCCO1>>[Br:1][C:2]1[N:3]=[C:4]([CH:7]2[CH2:8][CH2:9][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:11][CH2:12]2)[N:5]([CH2:21][CH2:22][OH:23])[CH:6]=1

Participants

3

Reactant 2

HCID 866212-(2-Bromoethoxy)tetrahydro-2H-pyranHCID 178451789HCID 178451789, compound2×

Product 1

HCID 67265139tert-Butyl 4-(4-bromo-1-(2-hydroxyethyl)-1H-imidazol-2-yl)piperidine-1-carboxylate

Procedure

tert-butyl 4-formylpiperidine-1-carboxylate 4a was reacted with aqueous glyoxal in the presence of aqueous ammonium hydroxide in methanol to give tert-butyl 4-(1H-imidazol-2-yl)piperidine-1-carboxylate 4b, which was bromined to afford tert-butyl 4-(4-bromo-1H-imidazol-2-yl)piperidine-1-carboxylate 4c. 4c was alkylated with 2-(2-bromoethoxy)tetrahydro-2H-pyran, followed by removal of THP group under acidic condition to yield tert-butyl 4-(4-bromo-1-(2-hydroxyethyl)-1H-imidazol-2-yl)piperidine-1-carboxylate 4d. Suzuki coupling was performed with bromide intermediate 4d to afford 4e. 4e was reacted with methanesulfonyl chloride or 4-methylbenzenesulfonyl chloride, followed by quenching with amine afforded 4f, which was treated with hydrogen chloride in methanol or trifloruoacetic acid in DCM to provide the amine intermediates 4g.

Workup

  1. customfollowed by removal of THP group under acidic condition

Sources & evidence

ORD record
ord-7f4c2a4903e244d0808e6bbc18b9a8ea
Source dataset
uspto-grants-2015_09
Patent number
US09145392B2

Reaction notes

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