3-Hydroxypyridine → 4-(3-Pyridyloxymethyl)2-phenylbenzoic acid methyl ester

HRID 2121195Notes

Reaction equation

HRID 2121195 reaction equation
[OH:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.C[Si](C)(C)[N-][Si](C)(C)C.[K+].C1OCCOCCOCCOCCOCCOC1.[CH3:36][O:37][C:38](=[O:53])[C:39]1[CH:44]=[CH:43][C:42]([CH2:45]Br)=[CH:41][C:40]=1[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1>COCCOC.C1(C)C=CC=CC=1.O>[CH3:36][O:37][C:38](=[O:53])[C:39]1[CH:44]=[CH:43][C:42]([CH2:45][O:1][C:2]2[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=2)=[CH:41][C:40]=1[C:47]1[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=1

Participants

8

Reactant 4

HCID 79713-HydroxypyridineHCID 2855718-Crown-6HCID 3251421Potassium bis(trimethylsilyl)amideHCID 18474540Methyl 4-bromomethyl-2-phenylbenzoate

Product 1

HCID 106870984-(3-Pyridyloxymethyl)2-phenylbenzoic acid methyl esterYield 48.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a mechanically-stirred 0° C. solution of 3-hydroxypyridine (4.4 g, 46 mmol) in DME (20 mL) was added potassium hexamethyldisilazide (0.5 M in toluene, 88.5 mL, 44 mmol) and the mixture was stirred for 15 minutes. 18-Crown-6 (1.46 g, 5.5 mmol) and a solution of 4-bromomethyl-2-phenylbenzoic acid methyl ester (6.8 g, 22 mmol) in toluene (25 mL) was added and the reaction mixture was vigorously stirred overnight. The reaction mixture was poured into 200 mL of water and the layers were separated. The aqueous phase was extracted with 2 portions of ethyl acetate and the combined organic phases were extracted with water and brine, dried (MgSO4), filtered and concentrated. The resulting oil was purified by flash chromatography (65% ethyl acetate-hexane) to give 4-(3-pyridyloxymethyl)-2-phenylbenzoic acid methyl ester (3.4 g).

Workup

  1. waitthe reaction mixture was vigorously stirred overnight
  2. customthe layers were separated
  3. extractionThe aqueous phase was extracted with 2 portions of ethyl acetate
  4. extractionthe combined organic phases were extracted with water and brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting oil was purified by flash chromatography (65% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-46f1714deabd407f83f5d6ccbca48c2c
Source dataset
uspto-grants-2004_02
Patent number
US06693123B2

Reaction notes

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