Sodium Carbonate → 1,4-dimethyl-5-(4-fluorophenyl)-1H-pyrrole-3-carboxylic acid ethyl ester

HRID 912584Notes

Reaction equation

Br[C:2]1[N:6]([CH3:7])[CH:5]=[C:4]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[C:3]=1[CH3:13].[F:14][C:15]1[CH:20]=[CH:19][C:18](B(O)O)=[CH:17][CH:16]=1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.O.C(Cl)Cl.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>[CH2:11]([O:10][C:8]([C:4]1[C:3]([CH3:13])=[C:2]([C:18]2[CH:19]=[CH:20][C:15]([F:14])=[CH:16][CH:17]=2)[N:6]([CH3:7])[CH:5]=1)=[O:9])[CH3:12]

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of ethyl 5-bromo-1,4-dimethyl-1H-pyrrole-3-carboxylate (246 mg, 1.0 mmol), 4-fluorophenyl-boronic acid (210 mg, 1.5 mmol), Na2CO3 (320 mg, 3.0 mmol) and Pd(PPh3)4 (116 mg, 0.10 mmol) in DMF/H2O (10:1, 10 mL) was sparged with nitrogen for 10 min. The reaction vial was sealed and heated at 110° C. with stirring. After 18h, the reaction mixture was diluted with DCM and then filtered. The filtrate was concentrated under reduced pressure and then purified by column chromatography, eluting with EtOAc-Hex (0:100 to 50:50), to give 1,4-dimethyl-5-(4-fluorophenyl)-1H-pyrrole-3-carboxylic acid ethyl ester (252 mg, 96%) as a pale yellow solid. 1H-NMR (CDCl3): δ 7.30 (1H, s), 7.26-7.20 (2H, m), 7.15-7.10 (2H, m), 4.28 (2H, q), 3.48 (3H, s), 2.20 (3H, s), 1.36 (3H, t). MS (ESI): 262 (MH+).

Workup

customwas sparged with nitrogen for 10 min
customThe reaction
customvial was sealed
filtrationfiltered
concentrationThe filtrate was concentrated under reduced pressure
custompurified by column chromatography
washeluting with EtOAc-Hex (0:100 to 50:50)

Sources & evidence

ORD record: ord-7b657cbe708245d9bb6df9f4b3ddabe9
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08026237B2

Reaction notes

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