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

HRID 383754Notes

Reaction equation

HRID 383754 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

7

Reactant 3

HCID 10340Sodium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 59808055ethyl 5-bromo-1,4-dimethyl-1H-pyrrole-3-carboxylate

Product 1

HCID 672531621,4-dimethyl-5-(4-fluorophenyl)-1H-pyrrole-3-carboxylic acid ethyl esterYield 96.4%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolventHCID 21962138N,N-Dimethylformamide--water (1/1)Solvent

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 18 h, 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+). The title compound was prepared from 1,4-dimethyl-5-(4-fluorophenyl)-1H-pyrrole-3-carboxylic acid ethyl ester in a manner similar to that described for Examples 16C-D.

Workup

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

Sources & evidence

ORD record
ord-4342a3d616584d9dba635ebd52539806
Source dataset
uspto-grants-2013_02
Patent number
US08367667B2

Reaction notes

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