Potassium Carbonate → tert-butyl 3-(2-bromo-5-(trifluoromethyl)phenyl)-2,5-dihydro-1H-pyrrole-1-carboxylate

HRID 1473365Notes

Reaction equation

HRID 1473365 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1I.CC1(C)C(C)(C)OB([C:21]2[CH2:22][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:24][CH:25]=2)O1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[C:25]1[CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][CH:21]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 15836637tert-Butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,5-dihydro-1H-pyrrole-1-carboxylateHCID 467352311-Bromo-2-iodo-4-(trifluoromethyl)benzene

Product 1

HCID 86687412tert-butyl 3-(2-bromo-5-(trifluoromethyl)phenyl)-2,5-dihydro-1H-pyrrole-1-carboxylateYield 62.1%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A solution of PdCl2(dppf)-CH2Cl2 adduct (0.349 g, 0.427 mmol), 1-bromo-2-iodo-4-(trifluoromethyl)benzene (1.500 g, 4.27 mmol), tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,5-dihydro-1H-pyrrole-1-carboxylate (ASW MedChem, Inc., New Brunswick, N.J., 1.893 g, 6.41 mmol), and potassium carbonate (3.54 g, 25.6 mmol) in 15 mL dioxane/7.5 mL water was heated to 100° C. for 1 hour. LC/MS showed product, so the reaction mixture was cooled to room temperature and the aqueous layer was removed. The organics were concentrated then purified directly by reverse phase column chromatography [Redisep Gold C18, 20-100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)] yielding tert-butyl 3-(2-bromo-5-(trifluoromethyl)phenyl)-2,5-dihydro-1H-pyrrole-1-carboxylate (1.040 g, 2.65 mmol, 62.0% yield). m/z (ESI) 413.9 (M+Na)+.

Workup

  1. customthe aqueous layer was removed
  2. concentrationThe organics were concentrated
  3. customthen purified directly by reverse phase column chromatography [Redisep Gold C18, 20-100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)]

Sources & evidence

ORD record
ord-9869c114e7ee48e18f23f5bd8d835373
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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