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

HRID 901981Notes

Reaction equation

HRID 901981 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-14e4cfaacc69434ea1f943a77ac9d4ba
Source dataset
uspto-grants-2008_04
Patent number
US07365070B2

Reaction notes

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