Water → 5-(2-Fluoro-pyridin-4-yl)-thiophene-3-carboxylic acid

HRID 2068650Notes

Reaction equation

Br[C:2]1[S:6][CH:5]=[C:4]([C:7]([OH:9])=[O:8])[CH:3]=1.[F:10][C:11]1[CH:16]=[C:15](B(O)O)[CH:14]=[CH:13][N:12]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>COCCOC.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]>[F:10][C:11]1[CH:16]=[C:15]([C:2]2[S:6][CH:5]=[C:4]([C:7]([OH:9])=[O:8])[CH:3]=2)[CH:14]=[CH:13][N:12]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 5-bromo-thiophene-3-carboxylic acid (0.71 g, 4.4 mmol), 2-fluoropyridine-4-boronic acid (0.619 g, 4.4 mmol), caesium carbonate (2.9 g, 8.8 mmol), and palladium tetrakis(triphenylphosphine) (0.469 g, 0.44 mmol) in DME (40 mL), IMS 20 mL) and water (10 mL) was divided across three microwave vials and each was heated by microwave irradiation to 120° C. for 20 minutes. The batches were combined and concentrated and the residue was partitioned between saturated aqueous sodium carbonate and DCM. The aqueous phase was isolated and filtered to obtain the title compound as a grey precipitate (0.168 g) and the filtrate was acidified using dilute HCl (pH 2) then re-filtered to obtain a further amount of the title compound as an off-white solid (0.114 g). LCMS m/z 224.06 [M+H]+ R.T.=2.77 min (Analytical Method 8).

Workup

concentrationconcentrated
customthe residue was partitioned between saturated aqueous sodium carbonate and DCM
customThe aqueous phase was isolated
filtrationfiltered

Sources & evidence

ORD record: ord-ebf8f8fc3e0d42cf91bf3ed0cc3df9c8
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08299063B2

Reaction notes

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