(3-Amino-4-chlorophenyl)methanol → 1-[2-chloro-5-(hydroxymethyl)phenyl]-4-hydroxy-6-methylpyridin-2(1H)-one

HRID 1867068Notes

Reaction equation

HRID 1867068 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[Cl:10])[CH2:5][OH:6].[OH:11][C:12]1[CH:17]=[C:16]([CH3:18])[O:15][C:14](=O)[CH:13]=1>ClC1C=CC=CC=1Cl>[Cl:10][C:9]1[CH:8]=[CH:7][C:4]([CH2:5][OH:6])=[CH:3][C:2]=1[N:1]1[C:16]([CH3:18])=[CH:17][C:12]([OH:11])=[CH:13][C:14]1=[O:15]

Participants

4

Reactant 2

HCID 13636475(3-Amino-4-chlorophenyl)methanolHCID 546757574-Hydroxy-6-methyl-2-pyrone

Product 1

HCID 547241841-[2-chloro-5-(hydroxymethyl)phenyl]-4-hydroxy-6-methylpyridin-2(1H)-oneYield 26%

Reagents, catalysts & solvents 1

HCID 72391,2-DichlorobenzeneSolvent

Procedure

3-amino-4-chloro-benzyl alcohol (8.0 g, 51.0 mmol) and 4-hydroxy-6-methyl-2-pyrone (6.4 g, 51.0 mmol) were taken up in 1,2-dichlorobenzene (50 ml). The mixture was plunged into a 165° C. oil bath where it stirred for 20 minutes. The reaction was cooled to room temperature and the reaction was worked up by washing with saturated NaHCO3 (aq.) and extracting impurities with ethyl acetate. The product remained in the aqueous layer. The basic aqueous layer was made acidic with concentrated HCl. The product was extracted from the acidic aqueous layer with ethyl acetate. The ethyl acetate layer was dried over Na2SO4 and the solvent removed in vacuo. The product was obtained as a yellow oil in a 26% yield and was carried through to the next step with no further purification. 1H NMR (300 MHz, CD3OD) δ 7.62 (d, J=8.26 Hz, 2H), 7.51 (dd, J=8.46, 2.22 Hz, 1H), 7.36 (d, J=2.01 Hz, 1H), 6.13 (br s, 1H), 5.84 (d, J=2.42 Hz, 1H), 4.68 (s, 2H), 1.97 (s, 3H); LC/MS, tr=0.25 minutes and 1.41 minutes (tautomer), (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50° C.). ES-MS m/z 266 (M+H).

Workup

  1. customwas plunged into a 165° C.
  2. washby washing with saturated NaHCO3 (aq.)
  3. extractionextracting impurities with ethyl acetate
  4. extractionThe product was extracted from the acidic aqueous layer with ethyl acetate
  5. dry with materialThe ethyl acetate layer was dried over Na2SO4
  6. customthe solvent removed in vacuo
  7. customThe product was obtained as a yellow oil in a 26% yield
  8. customwas carried through to the next step with no further purification
  9. customLC/MS, tr=0.25 minutes and 1.41 minutes (tautomer), (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50° C.)

Sources & evidence

ORD record
ord-64792487407842e49837177341fb0e7d
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

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