Hydrochloric Acid → HCID 23533987, compound

HRID 533709Notes

Reaction equation

HRID 533709 reaction equation
I[C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8]CC)=[O:7])=[CH:4][CH:3]=1.[F:13][C:14]1[CH:15]=[C:16]([C:20]#[CH:21])[CH:17]=[CH:18][CH:19]=1.C(NCC)C.[Li+].[OH-].Cl>CN(C=O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[F:13][C:14]1[CH:15]=[C:16]([C:20]#[C:21][C:2]2[CH:3]=[CH:4][C:5]([C:6]([OH:8])=[O:7])=[CH:11][CH:12]=2)[CH:17]=[CH:18][CH:19]=1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 8021DiethylamineHCID 142891Ethyl 4-iodobenzoateHCID 5202181-Ethynyl-3-fluorobenzene

Product 1

HCID 23533987HCID 23533987, compound

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of ethyl 4-Iodobenzoate (10.0 g, 36.2 mmol) in DMF (30 mL) was added 3-fluorophenylacetylene (5.22 g, 43.4 mmol), Pd(Ph3P)4 (1.04 g, 0.91 mmol), CuI (346 mg, 1.82 mmol) and diethylamine (6 mL). The reaction vessel was sealed and heated at 60° C. for 1 h in a microwave reactor. The reaction was cooled to room temperature, diluted with EtOAc:hexanes (2:1, 250 mL) and washed with water (2×200 mL) and brine (200 mL). The organic phase was dried over MgSO4, filtered and concentrated under vacuum. The crude product was dissolved in THF (130 mL) added MeOH (28 mL) and a solution of LiOH (3.04 g, 72.4 mmol) in water (28 mL). The reaction was stirred at room temperature and for 4 h. The reaction was acidified with 1 N HCl (100 mL) and 4-((3-fluorophenyl)ethynyl)benzoic acid was isolated (6.89 g, 79%) as a light tan solid; 1H-nmr (400 MHz, d6-DMSO) δ 7.97 (d, J=8.5 Hz, 2H), 7.68 (d, J=8.5 Hz, 1H), 7.55-7.42 (m, 3H), 7.21 (td, J=8.0, 2.0 Hz, 1H); LC (290 nM) 5.27 min (>98%); MS (ESI) m/z=240.7.

Workup

  1. customThe reaction vessel was sealed
  2. temperatureThe reaction was cooled to room temperature
  3. washwashed with water (2×200 mL) and brine (200 mL)
  4. dry with materialThe organic phase was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. dissolutionThe crude product was dissolved in THF (130 mL)
  8. additionadded MeOH (28 mL)

Sources & evidence

ORD record
ord-eccef76ebee14ababfa95656bc3e2552
Source dataset
uspto-grants-2014_10
Patent number
US08853392B2

Reaction notes

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