3,5-Dichloro-4-hydroxybenzoic acid → 2,6-Dichloro-4-[[[[3-[[(1,1-dimethylethyl)dimethyl-silyl]oxy]phenyl]methyl]amino]carbonyl]phenol

HRID 1726738Notes

Reaction equation

HRID 1726738 reaction equation
[CH3:1][C:2]([Si:5]([CH3:16])([CH3:15])[O:6][C:7]1[CH:8]=[C:9]([CH2:13][NH2:14])[CH:10]=[CH:11][CH:12]=1)([CH3:4])[CH3:3].[Cl:17][C:18]1[CH:19]=[C:20]([CH:24]=[C:25]([Cl:28])[C:26]=1[OH:27])[C:21](O)=[O:22].CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>ClCCl>[Cl:17][C:18]1[CH:19]=[C:20]([C:21]([NH:14][CH2:13][C:9]2[CH:10]=[CH:11][CH:12]=[C:7]([O:6][Si:5]([C:2]([CH3:1])([CH3:3])[CH3:4])([CH3:16])[CH3:15])[CH:8]=2)=[O:22])[CH:24]=[C:25]([Cl:28])[C:26]=1[OH:27]

Participants

6

Reactant 4

HCID 187493,5-Dichloro-4-hydroxybenzoic acidHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 222661693-[[(1,1-Dimethylethyl)dimethylsilyl]oxy]benzenemethanamine

Product 1

HCID 226613522,6-Dichloro-4-[[[[3-[[(1,1-dimethylethyl)dimethyl-silyl]oxy]phenyl]methyl]amino]carbonyl]phenolYield 87%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]benzenemethanamine (Example 8; 5.80 g, 24.5 mmol) in dry dichloromethane (20 mL) was added to a cooled (0° C.) suspension of 3,5-dichloro-4-hydroxybenzoic acid (4.2 g, 20.4 mmol) and BOP reagent (9.80 g, 22.3 mmol) in dry dichloromethane (50 mL). Diisopropylethylamine (10.6 mL, 60.9 mmol) was added slowly, and the cooling bath was removed. The solution was stirred at room temperature for 5 h, then the solvent was evaporated and the residue was dissolved in ethyl acetate. The solution was washed with 1 M HCl (2×100 mL), saturated aqueous sodium hydrogen carbonate (100 mL), and brine (100 mL), dried (MgSO4), filtered, evaporated, and chromatographed (30% ethyl acetate/hexanes) to give 2,6-dichloro-4-[[[[3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]phenyl]methyl]amino]carbonyl]phenol (7.50 g, 87%) as a white solid.

Workup

  1. temperaturea cooled
  2. customthe cooling bath was removed
  3. customthe solvent was evaporated
  4. dissolutionthe residue was dissolved in ethyl acetate
  5. washThe solution was washed with 1 M HCl (2×100 mL), saturated aqueous sodium hydrogen carbonate (100 mL), and brine (100 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customevaporated
  9. customchromatographed (30% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-bedb3c7d481f49ee95b6237c45100598
Source dataset
uspto-grants-2009_02
Patent number
US07491741B2

Reaction notes

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