4-(Hydroxymethyl)benzoic acid → HCID 59509485, compound

HRID 2407478Notes

Reaction equation

HRID 2407478 reaction equation
O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[OH:24][CH2:25][C:26]1[CH:34]=[CH:33][C:29]([C:30]([OH:32])=O)=[CH:28][CH:27]=1.[F:35][C:36]1[CH:41]=[C:40]([C:42]([NH:44]O)=[NH:43])[CH:39]=[CH:38][C:37]=1[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1>O.CN(C)C=O>[F:35][C:36]1[CH:41]=[C:40]([C:42]2[N:43]=[C:30]([C:29]3[CH:28]=[CH:27][C:26]([CH2:25][OH:24])=[CH:34][CH:33]=3)[O:32][N:44]=2)[CH:39]=[CH:38][C:37]=1[C:46]1[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=1

Participants

7

Reactant 4

HCID 763604-(Hydroxymethyl)benzoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 178513264HCID 178513264, compound

Product 1

HCID 59509485HCID 59509485, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
135 °C

Procedure

1-Hydroxybenzotriazole hydrate (1.35 g, 0.01 mol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide HCl (1.95 g, 0.01 mol) are added to a stirred N,N-dimethylformamide solution (20 mL) of 4-hydroxymethylbenzoic acid (1.52 g, 0.01 mol). 2-Fluoro-N-hydroxybiphenyl-4-carboxamidine (2.3 g, 0.01 mol) is added to the reaction mixture which is then heated at 130-140° C. for 4 hrs. The reaction mixture is cooled to room temperature, Demineralized water (60 mL) is added and the aqueous layer is extracted with ethyl acetate (3×20 mL). Combined organic layers are washed with demineralized water (2×10 mL) followed by brine (1×20 mL) and finally dried over sodium sulphate. Removal of ethyl acetate under reduced pressure gives a crude liquid which is purified by column chromatography (silica gel 230-400 mesh, ethyl acetate:n-hexane 30:70) to furnish {4-[3-(2-fluorobiphenyl-4-yl)-1,2,4-oxadiazol-5-yl]phenyl}methanol.

Workup

  1. temperatureThe reaction mixture is cooled to room temperature
  2. extractionthe aqueous layer is extracted with ethyl acetate (3×20 mL)
  3. washCombined organic layers are washed with demineralized water (2×10 mL)
  4. dry with materialfinally dried over sodium sulphate
  5. customRemoval of ethyl acetate under reduced pressure
  6. customgives a crude liquid which
  7. customis purified by column chromatography (silica gel 230-400 mesh, ethyl acetate:n-hexane 30:70)

Sources & evidence

ORD record
ord-74f388384c924dd7a4da401ba2293fe5
Source dataset
uspto-grants-2014_08
Patent number
US08809539B2

Reaction notes

Loading…