Hydrochloric Acid → HCID 66559225, compound

HRID 2405958Notes

Reaction equation

HRID 2405958 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[C:10]1[N:11]=[N:12][N:13]([CH2:15][CH2:16][C@@:17]([CH3:32])([S:28]([CH3:31])(=[O:30])=[O:29])[C:18]([NH:20][O:21]C2CCCCO2)=[O:19])[CH:14]=1.Cl>CCO>[Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[C:10]1[N:11]=[N:12][N:13]([CH2:15][CH2:16][C@@:17]([CH3:32])([S:28]([CH3:31])(=[O:29])=[O:30])[C:18]([NH:20][OH:21])=[O:19])[CH:14]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86710256HCID 86710256, compound

Product 1

HCID 66559225HCID 66559225, compoundYield 67.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 2-chloro-1-ethynyl-4-methoxybenzene (15 mg, 0.093 mmol, 1 eq) and (2R)-4-azido-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide (30 mg 0.093 mmol, 1 eq) in EtOH—H2O (7 mL:1 mL) was added sodium ascorbate (19 mg, 0.093 mmol, 1 eq) and CuSO4 (9 mg, 0.037 mmol, 0.4 eq). The reaction mixture was stirred vigorously at RT overnight. The reaction mixture was concentrated to remove the EtOH/H2O. The residue was dissolved in EtOAc and the CuSO4 solid was filtered off. The filtrated was adsorbed onto silica and purified by flash chromatography on a 12 g silica gel column eluting with 0-100% EtOAc/Hpt to give (2R)-4-[4-(2-chloro-4-methoxyphenyl)-1H-1,2,3-triazol-1-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide (18 mg). To a solution of (2R)-4-[4-(2-chloro-4-methoxyphenyl)-1H-1,2,3-triazol-1-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide (18 mg, 0.037 mmol, 1 eq) in EtOH (93 mL) was added 4 M HCl. The reaction mixture was allowed to stir at RT for 3 h and then concentrated to give (2R)-4-[4-(2-chloro-4-methoxyphenyl)-1H-1,2,3-triazol-1-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide (10 mg, 67% yield). 1H NMR (400 MHz, METHANOL-d4) δ 8.69 (s, 1H), 7.80 (d, J=8.6 Hz, 1H), 7.15 (d, J=2.5 Hz, 1H), 7.09-7.02 (m, 1H), 4.85-4.73 (m, 1H), 4.71-4.57 (m, 1H), 3.87 (s, 3H), 3.07 (s, 4H), 2.63-2.50 (m, 1H), 1.69 (s, 3H). LC-MS M+H+403.1.

Workup

  1. concentrationconcentrated

Sources & evidence

ORD record
ord-b74ed16bbb31417fbe9667e491069f40
Source dataset
uspto-grants-2014_08
Patent number
US08809333B2

Reaction notes

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