3-(4-Fluorophenyl)propionic acid → Methyl 3-(4-fluorophenyl)propanoate

HRID 1508553Notes

Reaction equation

HRID 1508553 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([OH:12])=[O:11])=[CH:4][CH:3]=1.[CH3:13][Si](C=[N+]=[N-])(C)C>C1(C)C=CC=CC=1.CO>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][CH2:9][C:10]([O:12][CH3:13])=[O:11])=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 1363023-(4-Fluorophenyl)propionic acidHCID 167693Trimethylsilyldiazomethane

Product 1

HCID 22906572Methyl 3-(4-fluorophenyl)propanoate

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1140TolueneSolvent

Procedure

To a solution of 3-(4-fluorophenyl)propionic acid (4.75 g, 28.2 mmol) in toluene (130 mL) and methanol (20 mL) was added trimethylsilyldiazomethane (2M solution in hexane, 16.24 mL, 32.5 mmol). The mixture was allowed to stir for 1 hour and gas evolution was observed initially. After 1 hour, the mixture became homogeneous and was quenched via addition of 3.5 mL of acetic acid. The mixture was concentrated in vacuo, and purified via column chromatography on a Biotage 65i column eluting with 0% ethyl acetate in hexanes (1 CV) followed by a gradient to 50% ethyl acetate in hexanes (over 7 CV) to furnish the desired product. 1H NMR (CDCl3, 500 MHz) δ 7.16 (dd, J=8.0 Hz, 5.6 Hz, 2H), 6.97 (t, J=8.5 Hz, 2H), 3.66 (s, 3H), 2.92 (t, J=7.5 Hz, 2H), 2.61 (t, J=7.7 Hz, 2H).

Workup

  1. waitAfter 1 hour
  2. customwas quenched via addition of 3.5 mL of acetic acid
  3. concentrationThe mixture was concentrated in vacuo
  4. custompurified via column chromatography on a Biotage 65i column
  5. washeluting with 0% ethyl acetate in hexanes (1 CV)

Sources & evidence

ORD record
ord-5d94160db8c84f508a15f83e02dc9584
Source dataset
uspto-grants-2015_12
Patent number
US09221834B2

Reaction notes

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