Formaldehyde → 4-{[(2-Fluoro-4-hydroxy-phenyl)-methyl-amino]-methyl}-2-methyl-benzoic Acid Methyl Ester

HRID 424819Notes

Reaction equation

HRID 424819 reaction equation
[CH3:1][O:2][C:3](=[O:21])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][NH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][C:13]=2[F:19])=[CH:6][C:5]=1[CH3:20].C=O.[C:24](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(O)(=O)C>[CH3:1][O:2][C:3](=[O:21])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][N:11]([C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][C:13]=2[F:19])[CH3:24])=[CH:6][C:5]=1[CH3:20]

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 667041774-[(2-Fluoro-4-hydroxy-phenylamino)-methyl]-2-methyl-benzoic Acid Methyl Ester

Product 1

HCID 574433514-{[(2-Fluoro-4-hydroxy-phenyl)-methyl-amino]-methyl}-2-methyl-benzoic Acid Methyl EsterYield 51%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A mixture of 4-[(2-fluoro-4-hydroxy-phenylamino)-methyl]-2-methyl-benzoic acid methyl ester (1.89 g, 6.53 mmol) and 37% formaldehyde (2.0 mL) in acetic acid (20 mL) is stirred for 40 minutes. Sodium triacetoxyborohydride (2.80 g, 13.2 mmol) is added and stirred at room temperature. Upon completion of the reaction, the mixture is concentrated and partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The aqueous layer is separated and extracted with ethyl acetate (3×). The combined ethyl acetate layers are dried (MgSO4) and concentrated under reduced pressure. The residue is purified on 120 g silica eluting with a gradient of ethyl acetate in heptane (10% to 60%) to provide the titled compound (1.0 g, 51%) as a white solid. LC-ES/MS m/e 304.0 (M+1).

Workup

  1. stirringstirred at room temperature
  2. customUpon completion of the reaction
  3. concentrationthe mixture is concentrated
  4. custompartitioned between ethyl acetate and saturated aqueous sodium bicarbonate
  5. customThe aqueous layer is separated
  6. extractionextracted with ethyl acetate (3×)
  7. dry with materialThe combined ethyl acetate layers are dried (MgSO4)
  8. concentrationconcentrated under reduced pressure
  9. customThe residue is purified on 120 g silica eluting with a gradient of ethyl acetate in heptane (10% to 60%)

Sources & evidence

ORD record
ord-db44e3c45e3541b8ba8db30b5579df5d
Source dataset
uspto-grants-2012_01
Patent number
US08106077B2

Reaction notes

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