4-Hydroxy-3,5-dimethylbenzoic acid → 3,5-dimethyl-N-[3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]benzyl]-4-hydroxybenzamide

HRID 1058399Notes

Reaction equation

HRID 1058399 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([CH3:12])[C:10]=1[OH:11])[C:5]([OH:7])=O.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[CH3:40][C:41]([Si:44]([CH3:55])([CH3:54])[O:45][C:46]1[CH:47]=[C:48]([CH2:52][NH2:53])[CH:49]=[CH:50][CH:51]=1)([CH3:43])[CH3:42]>ClCCl>[CH3:12][C:9]1[CH:8]=[C:4]([CH:3]=[C:2]([CH3:1])[C:10]=1[OH:11])[C:5]([NH:53][CH2:52][C:48]1[CH:49]=[CH:50][CH:51]=[C:46]([O:45][Si:44]([C:41]([CH3:43])([CH3:42])[CH3:40])([CH3:54])[CH3:55])[CH:47]=1)=[O:7]

Participants

5

Reactant 3

HCID 1383874-Hydroxy-3,5-dimethylbenzoic acidHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 222661693-[[(1,1-Dimethylethyl)dimethylsilyl]oxy]benzenemethanamine

Product 1

HCID 186730413,5-dimethyl-N-[3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]benzyl]-4-hydroxybenzamideYield 87.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of 3,5-dimethyl-4-hydroxybenzoic acid (1.53 g, 9.2 mmol) in dichloromethane (30 mL) at 0° C. was added benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (4.45 g, 10 mmol), 3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]benzenemethanamine (Example 70; 3.28 g, 13.8 mmol), followed by diisopropylethylamnine (4.9 mL, 27.6 mmol) slowly dropwise. After stirring 1 h, the reaction was warmed to 25° C. and stirred for 1 h. The solvent was removed under reduced pressure and the residual oil was diluted with ethyl acetate (100 mL) and washed with 1N hydrochloric acid solution (2×25 mL), saturated aqueous sodium bicarbonate solution (2×25 mL), water (25 mL) and brine (25 mL). The organic layer was dried (MgSO4), filtered, evaporated and flash chromatographed (silica gel, 20-30% ethyl acetate in petroleum ether) to give 3,5-dimethyl-N-[3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]benzyl]-4-hydroxybenzamide (3.1 g, 87% yield) as an off-white foam.

Workup

  1. stirringstirred for 1 h
  2. customThe solvent was removed under reduced pressure
  3. additionthe residual oil was diluted with ethyl acetate (100 mL)
  4. washwashed with 1N hydrochloric acid solution (2×25 mL), saturated aqueous sodium bicarbonate solution (2×25 mL), water (25 mL) and brine (25 mL)
  5. dry with materialThe organic layer was dried (MgSO4)
  6. filtrationfiltered
  7. customevaporated
  8. customflash chromatographed (silica gel, 20-30% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-fa1863e6334f46bcb778f7fcbb1ba493
Source dataset
uspto-grants-2003_02
Patent number
US06515124B2

Reaction notes

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