Hydrochloric Acid → 4-{[(2-Fluoro-4-hydroxy-6-methyl-phenyl)-methyl-amino]-methyl}-2-methyl-benzoic acid methyl ester

HRID 2261837Notes

Reaction equation

HRID 2261837 reaction equation
[CH3:1][O:2][C:3](=[O:33])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][N:11]([C:13]2[C:18]([CH3:19])=[CH:17][C:16]([O:20][Si](C(C)C)(C(C)C)C(C)C)=[CH:15][C:14]=2[F:31])[CH3:12])=[CH:6][C:5]=1[CH3:32].[F-].C([N+](CCCC)(CCCC)CCCC)CCC.Cl>C1COCC1>[CH3:1][O:2][C:3](=[O:33])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][N:11]([C:13]2[C:18]([CH3:19])=[CH:17][C:16]([OH:20])=[CH:15][C:14]=2[F:31])[CH3:12])=[CH:6][C:5]=1[CH3:32]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 2724141Tetrabutylammonium FluorideHCID 574433494-{[(2-Fluoro-6-methyl-4-triisopropylsilanyloxy-phenyl)-methyl-amino]-methyl}-2-methyl-benzoic acid methyl ester

Product 1

HCID 675280644-{[(2-Fluoro-4-hydroxy-6-methyl-phenyl)-methyl-amino]-methyl}-2-methyl-benzoic acid methyl esterYield 76.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 4-{[(2-fluoro-6-methyl-4-triisopropylsilanyloxy-phenyl)-methyl-amino]-methyl}-2-methyl-benzoic acid methyl ester (457 mg, 0.965 mmol) and tetrabutylammonium fluoride (2.0 mL of 1M in THF, 2.0 mmol) in THF (10 mL) is stirred at 0° C. for 20 minutes and then 2.0 mL of 1M HCl is added and the mixture is concentrated. The residue is portioned between ethyl acetate and brine. The layers are separated and the brine layer is extracted with ethyl acetate. The combined ethyl acetate layers are dried (MgSO4) and concentrated. The residue is purified on 40 g silica with ethyl acetate in heptane gradient (10% to 70%) to provide 233 mg (76%) of the titled compound as a glass. LC-ES/MS m/e 318.2 (M+1).

Workup

  1. concentrationthe mixture is concentrated
  2. customThe layers are separated
  3. extractionthe brine layer is extracted with ethyl acetate
  4. dry with materialThe combined ethyl acetate layers are dried (MgSO4)
  5. concentrationconcentrated
  6. customThe residue is purified on 40 g silica with ethyl acetate in heptane gradient (10% to 70%)

Sources & evidence

ORD record
ord-f2758d59b18d41259792b9ea7dad92b1
Source dataset
uspto-grants-2010_12
Patent number
US07846960B2

Reaction notes

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