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

HRID 2261838Notes

Reaction equation

HRID 2261838 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 2.0 mL of 37% formaldehyde in 20 mL of acetic acid is stirred for 40 minutes. Sodium triacetoxyborohydride (2.80 g, 13.2 mmol) is added. Upon completion, the mixture is concentrated and partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The aqueous layer is extracted with ethyl acetate (3×). The combined ethyl acetate layers are dried (MgSO4) and concentrated. The residue is purified on 120 g silica with ethyl acetate in heptane gradient (10% to 60%) to provide 1.0 g (51%) of the titled compound as a white solid. LC-ES/MS m/e 304.0 (M+1).

Workup

  1. concentrationUpon completion, the mixture is concentrated
  2. custompartitioned between ethyl acetate and saturated aqueous sodium bicarbonate
  3. extractionThe aqueous layer is extracted with ethyl acetate (3×)
  4. dry with materialThe combined ethyl acetate layers are dried (MgSO4)
  5. concentrationconcentrated
  6. customThe residue is purified on 120 g silica with ethyl acetate in heptane gradient (10% to 60%)

Sources & evidence

ORD record
ord-0ea83511e61d47318125dd346371361e
Source dataset
uspto-grants-2010_12
Patent number
US07846960B2

Reaction notes

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