Benzene, 2-chloro-1-ethynyl-4-methoxy- → HCID 86710256, compound

HRID 2405957Notes

Reaction equation

HRID 2405957 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[C:10]#[CH:11].[N:12]([CH2:15][CH2:16][C@@:17]([CH3:32])([S:28]([CH3:31])(=[O:30])=[O:29])[C:18]([NH:20][O:21][CH:22]1[CH2:27][CH2:26][CH2:25][CH2:24][O:23]1)=[O:19])=[N+:13]=[N-:14].O=C1O[C@H]([C@H](CO)O)C([O-])=C1O.[Na+]>C(O)C.O.[O-]S([O-])(=O)=O.[Cu+2]>[Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[C:10]1[N:14]=[N:13][N:12]([CH2:15][CH2:16][C@@:17]([CH3:32])([S:28]([CH3:31])(=[O:30])=[O:29])[C:18]([NH:20][O:21][CH:22]2[CH2:27][CH2:26][CH2:25][CH2:24][O:23]2)=[O:19])[CH:11]=1

Participants

6

Reactant 3

HCID 18953717Benzene, 2-chloro-1-ethynyl-4-methoxy-HCID 23667548Sodium AscorbateHCID 71477855HCID 71477855, compound

Product 1

HCID 86710256HCID 86710256, compoundYield 39.7%

Reagents, catalysts & solvents 2

HCID 24462Copper SulfateCatalystHCID 19096565Water ethanolSolvent

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. concentrationThe reaction mixture was concentrated
  2. customto remove the EtOH/H2O
  3. dissolutionThe residue was dissolved in EtOAc
  4. filtrationthe CuSO4 solid was filtered off
  5. custompurified by flash chromatography on a 12 g silica gel column
  6. washeluting with 0-100% EtOAc/Hpt

Sources & evidence

ORD record
ord-692ec40a7f534f759097a50187c24d3d
Source dataset
uspto-grants-2014_08
Patent number
US08809333B2

Reaction notes

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