N,N,N',N'-Tetramethylethylenediamine → HCID 68504850, compound

HRID 1710441Notes

Reaction equation

HRID 1710441 reaction equation
[F:1][C:2]1[C:3]([CH3:11])=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=[O:6].CN(C)CCN(C)C.[Li]C(CC)C.[Br:25][C:26]1[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][C:27]=1[CH2:28]Br>C1COCC1>[Br:25][C:26]1[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][C:27]=1[CH2:28][CH2:11][C:3]1[C:2]([F:1])=[CH:10][CH:9]=[CH:8][C:4]=1[C:5]([OH:7])=[O:6]

Participants

6

Reactant 4

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 2466823-Fluoro-2-methylbenzoic acidHCID 35259512-Bromo-5-methoxybenzyl bromideHCID 178418400CID 53628100

Product 1

HCID 68504850HCID 68504850, compoundYield 80%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 3-fluoro-2-methylbenzoic acid (5.00 g, 32 mmol, 1 equiv) and N,N,N′,N′-tetramethylethylenediamine (TMEDA) (9.7 mL, 64 mmol, 2 equiv) in THF (100 mL) was cooled to −78° C. under an atmosphere of argon. s-BuLi (1.3 M in hexanes, 52 mL, 26 mmol, 2.1 equiv) was added dropwise and the solution was allowed to stir for 1 hr. A solution of 2-bromo-5-methoxybenzylbromide (22 g, 80 mmol, 2.5 equiv) in THF (10 mL) was added dropwise. The solution was allowed stir for 1 hr at −78° C. hr and then quenched by the addition of H2O and 1N HCl. The mixture was extracted with ethyl acetate. The combined organic phases were washed with brine, dried over MgSO4, filtered, and concentrated. After column chromatography (SiO2) followed by trituration from MeOH/DCM, 2-[2-(2-bromo-5-methoxy-phenyl)-ethyl]-3-fluoro-benzoic acid (3.3 g, 9.4 mmol, 80%) was obtained as a white powder. 1H NMR (300 MHz, CDCl3) δ 7.66 (d, J=7.8 Hz, 1H), 7.12-7.33 (m, 4H), 6.78 (d, J=9.0 Hz, 1H), 3.76 (s, 3H), 3.24 (t, J=7.5 Hz, 2H), 2.83 (t, J=7.5 Hz, 2H). LCMS: ES− 351 (M−1), 353 (M+1), 355 (M+3).

Workup

  1. stirringThe solution was allowed stir for 1 hr at −78° C. hr
  2. customquenched by the addition of H2O and 1N HCl
  3. extractionThe mixture was extracted with ethyl acetate
  4. washThe combined organic phases were washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-acf9cc5cb940492d8d262a53b7679ea2
Source dataset
uspto-grants-2010_09
Patent number
US07790719B2

Reaction notes

Loading…