4-Hydroxybenzoic Acid → 4-[(tert-Butyldimethylsilyl)oxy]benzoic acid

HRID 61963Notes

Reaction equation

HRID 61963 reaction equation
[OH:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[Si:20](Cl)([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:22])[CH3:21].OP(O)(O)=O>CN(C=O)C.C(Cl)Cl.CO>[Si:20]([O:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1)([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:22])[CH3:21]

Participants

8

Reactant 4

HCID 1354-Hydroxybenzoic AcidHCID 1004Phosphoric AcidHCID 28928tert-Butyldimethylsilyl chlorideHCID 81531Diisopropylethylamine

Product 1

HCID 109011414-[(tert-Butyldimethylsilyl)oxy]benzoic acidYield 53,000%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To prepare 22, a solution of 4-hydroxybenzoic acid (21, 1.52 g, 10 mmol) in DMF (7 ml) was treated with DIPEA (5.2 ml, 30 mmol) and tert-butyldimethylsilyl chloride (3.7 g, 24.5 mmol). After 12 hours, the mixture was brought to a pH of 4 by addition of 1 M H3PO4. The mixture was extracted twice with hexanes (15 ml). The organic phase was washed twice with water (15 ml), dried over Na2SO4, and concentrated in vacuum. The residue (3.7 g) was dissolved in THF (10 ml), and treated with water (7 ml) and glacial acetic acid (21 ml). After stirring for 90 minutes, the mixture was added to ice water and extracted twice with a 1:1 mixture (v/v) of diethyl ether and hexanes (30 ml). The organic phase was washed with water (30 ml), dried over Na2SO4, and concentrated in vacuum. Flash column chromatography on silica using a gradient of 5-20% methanol in DCM containing 0.2% acetic acid afforded 4-tert-butyldimethylsilyloxybenzoic acid (22, 1.42 g, 5.3 mol, 53%) as a white solid. 1H NMR (400 MHz, chloroform-d1): δ (ppm) 0.24 (s, 6H), 0.99 (s, 9H), 6.89 (d, J=8.8 Hz, 2H), 8.02 (d, J=8.8 Hz, 2H); 13C NMR (100 MHz, chloroform-d1): δ (ppm)-4.22, 18.40, 25.73, 120.08, 122.39, 132.46, 132.46, 161.01, 172.23. See FIGS. 33A-B.

Workup

  1. customTo prepare 22
  2. extractionThe mixture was extracted twice with hexanes (15 ml)
  3. washThe organic phase was washed twice with water (15 ml)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuum
  6. dissolutionThe residue (3.7 g) was dissolved in THF (10 ml)
  7. additiontreated with water (7 ml) and glacial acetic acid (21 ml)
  8. additionthe mixture was added to ice water
  9. extractionextracted twice with a 1:1 mixture (v/v) of diethyl ether and hexanes (30 ml)
  10. washThe organic phase was washed with water (30 ml)
  11. dry with materialdried over Na2SO4
  12. concentrationconcentrated in vacuum

Sources & evidence

ORD record
ord-0eaedb2a6a374ed7832cad69cb530dc5
Source dataset
uspto-grants-2016_09
Patent number
US09445596B2

Reaction notes

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