Diisopropylethylamine → 4-(5-{3-[3-(4-Fluorophenyl)prop-1-ynyl]phenyl}tetrazol-2-ylmethyl)benzene-sulfonic acid

HRID 349454Notes

Reaction equation

HRID 349454 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]2[N:9]=[N:10][N:11]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([S:20]([OH:23])(=[O:22])=[O:21])=[CH:16][CH:15]=3)[N:12]=2)[CH:5]=[CH:6][CH:7]=1.[Na].C(N(C(C)C)CC)(C)C.[F:34][C:35]1[CH:40]=[CH:39][C:38]([CH2:41][C:42]#[CH:43])=[CH:37][CH:36]=1>CN(C=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd].[Cu]I>[F:34][C:35]1[CH:40]=[CH:39][C:38]([CH2:41][C:42]#[C:43][C:2]2[CH:3]=[C:4]([C:8]3[N:9]=[N:10][N:11]([CH2:13][C:14]4[CH:19]=[CH:18][C:17]([S:20]([OH:23])(=[O:22])=[O:21])=[CH:16][CH:15]=4)[N:12]=3)[CH:5]=[CH:6][CH:7]=2)=[CH:37][CH:36]=1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 5360545SodiumHCID 105586681-Fluoro-4-prop-2-ynyl-benzeneHCID 865913364-[5-(3-Bromophenyl)tetrazol-2-ylmethyl]benzenesulfonic acid

Product 1

HCID 865913354-(5-{3-[3-(4-Fluorophenyl)prop-1-ynyl]phenyl}tetrazol-2-ylmethyl)benzene-sulfonic acidYield 8.26%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of 4-[5-(3-bromophenyl)tetrazol-2-ylmethyl]benzenesulfonic acid, sodium salt (0.50 g, 1.27 mmol) in DMF (3 mL) was treated with diisopropylethylamine (0.88 mL, 5.1 mmol), palladium tetrakis(triphenylphosphine) (“Pd(PPh3)4”, 0.29 g, 0.25 mmol), CuI (cat), and 1-fluoro-4-prop-2-ynyl-benzene (0.42 g, 3.1 mmol), and the mixture degassed with nitrogen. The reaction mixture was heated in the microwave for 15 minutes at 100° C., cooled to room temperature, poured into 1N HCl, extracted with EtOAc, washed with brine, dried over MgSO4, and evaporated onto silica gel. The mesh was purified on a 3.5×15 cm silica gel column eluted with ethyl acetate (“EtOAc”)-methanol (“MeOH”) 4:1 with 1% acetic acid (“AcOH”). Evaporation and trituration with ether afforded 0.052 g of orange solid (8.26% yield) NMR (DMSO-d6); 8.03–7.99 (m, 1H), 7.61–7.51 (m, 6H), 7.46–7.42 (dd, 1H), 7.36–7.33 (d, 2H), 7.19–7.15 (t, 2H), 5.98 (s, 2H), 3.90 (s, 2H)

Workup

  1. customthe mixture degassed with nitrogen
  2. temperaturecooled to room temperature
  3. additionpoured into 1N HCl
  4. extractionextracted with EtOAc
  5. washwashed with brine
  6. dry with materialdried over MgSO4
  7. customevaporated onto silica gel
  8. customThe mesh was purified on a 3.5×15 cm silica gel column
  9. washeluted with ethyl acetate (“EtOAc”)-methanol (“MeOH”) 4:1 with 1% acetic acid (“AcOH”)
  10. customEvaporation and trituration with ether

Sources & evidence

ORD record
ord-ebb5809445cd41b295913ee4168b6e8f
Source dataset
uspto-grants-2007_02
Patent number
US07179822B2

Reaction notes

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