Trimethylsilyldiazomethane → Methyl 2-(3-cyano-4-fluorophenyl)acetate

HRID 1810098Notes

Reaction equation

HRID 1810098 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH2:10][C:11]([OH:13])=[O:12])[CH:6]=[CH:7][C:8]=1[F:9])#[N:2].[Si](C=[N+]=[N-])(C)(C)[CH3:15]>C1COCC1.CO>[C:1]([C:3]1[CH:4]=[C:5]([CH2:10][C:11]([O:13][CH3:15])=[O:12])[CH:6]=[CH:7][C:8]=1[F:9])#[N:2]

Participants

5

Reactant 2

HCID 167693TrimethylsilyldiazomethaneHCID 27739352-(3-Cyano-4-fluorophenyl)acetic acid

Product 1

HCID 68513176Methyl 2-(3-cyano-4-fluorophenyl)acetateYield 41%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

2-(3-Cyano-4fluorophenyl)acetic acid (4.0 g, 22.3 mmol) was diluted with THF (10 mL) and methanol (2 mL), placed under nitrogen and cooled to 0° C. TMSCHN2 (16.7 mL, 33.5 mmol) was added dropwise and the reaction was stirred for 30 minutes. The reaction was quenched with water and diluted with DCM. The layers were separated and the organic layer was dried over MgSO4, filtered and concentrated. The residue was purified using a Biotage 40M cartridge eluting with hexanes ethyl acetate (9.1) to yield methyl 2(3-cyano-4-fluorophenyl)acetate (1.76 g, 9.11 mmol, 41%) as clear oil that solidified to a white solid. 1H NMR (400 MHz, CDCl3) δ 7.48-7.59 (m, 2H), 7.19 (t, J=8.2 Hz, 1H), 3.73 (s, 3H), 3.64 (s, 2H).

Workup

  1. customThe reaction was quenched with water
  2. additiondiluted with DCM
  3. customThe layers were separated
  4. dry with materialthe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified
  8. washeluting with hexanes ethyl acetate (9.1)

Sources & evidence

ORD record
ord-440d0855fd1d4a42951b652bb0181704
Source dataset
uspto-grants-2013_01
Patent number
US08362056B2

Reaction notes

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