Ethanol → Methyl 4-(4-(tert-butoxycarbonylamino)phenyl)-1-methyl-1H-pyrrole-2-carboxylate

HRID 632966Notes

Reaction equation

HRID 632966 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]([O:10][CH3:11])=[O:9])[N:5]([CH3:7])[CH:6]=1.[C:12]([O:16][C:17]([NH:19][C:20]1[CH:25]=[CH:24][C:23](B(O)O)=[CH:22][CH:21]=1)=[O:18])([CH3:15])([CH3:14])[CH3:13].CCO.C([O-])([O-])=O.[K+].[K+]>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.C1(C)C=CC=CC=1>[C:12]([O:16][C:17]([NH:19][C:20]1[CH:25]=[CH:24][C:23]([C:2]2[CH:3]=[C:4]([C:8]([O:10][CH3:11])=[O:9])[N:5]([CH3:7])[CH:6]=2)=[CH:22][CH:21]=1)=[O:18])([CH3:15])([CH3:13])[CH3:14]

Participants

8

Reactant 4

HCID 702EthanolHCID 11430Potassium CarbonateHCID 3613184(4-Boc-Aminophenyl)Boronic AcidHCID 11424498Methyl 4-bromo-1-methyl-1H-pyrrole-2-carboxylate

Product 1

HCID 67253196Methyl 4-(4-(tert-butoxycarbonylamino)phenyl)-1-methyl-1H-pyrrole-2-carboxylateYield 97%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 962WaterSolvent2×HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A catalytic amount of tetrakis(triphenylphosphine)palladium, Pd(PPh3)4 (0.477 g, 0.413, 0.06 eq) was added to a solution of 4 (1.5 g, 6.88 mmol, 1 eq) and (4-((tert-butoxycarbonyl)amino)phenyl)boronic acid (1.57 g, 6.88 mmol, 1.20 eq) in a 9:3:1 combination (13.5 ml) of EtOH, toluene and water in the presence of K2CO3 (2.856 g, 3 eq.) in a 10-20 mL microwave vial containing a magnetic stirrer. The reaction vessel was flushed with nitrogen during each addition. The reaction mixture was sealed in an inert N2 atmosphere and heated with microwave radiation in an EMRYS™ Optimizer Microwave Station (Personal Chemistry) at 100° C. for 12 minutes. After LCMS and TLC analysis revealed completion of the reaction, the cooled reaction mixture was diluted with water (50 mL), extracted with EtOAc (3×40 mL), the filtrates combined, dried over MgSO4 and concentrated under vacuum. The resulting oil was subjected to flash chromatography (n-hexane/EtOAc 9:1) to give 5 (Yield—2.2 g, 97%). IR (FTIR, vmax/cm−1): 3353, 2975, 1696, 1521, 1441, 1366, 1264, 1235, 1209, 1058, 822, 799, 657; 1H-NMR (400 MHz, CDCl3): δ 7.40 (d, 2H, J=8.8 Hz), 7.33 (d, 2H, J=8.8 Hz), 7.16 (d, 1H, J=2.0 Hz), 7.02 (d, 1H, J=2.0), 6.45 (br s, 1H), 3.95 (s, 3H), 3.83 (s, 3H), 1.52 (s, 9H); 13C-NMR (100 MHz, CDCl3): δ 161.7, 152.8, 136.5, 129.5, 125.9, 125.6, 123.7, 123.0, 119.0, 114.6, 80.5, 51.1, 36.9, 28.4; EIMS m/z (+EI) calc. for C18H22N2O4 (M)+ 330.38. found 330.46 (M+H)+

Workup

  1. additioncontaining a magnetic stirrer
  2. customThe reaction vessel was flushed with nitrogen during each addition
  3. customThe reaction mixture was sealed in an inert N2 atmosphere
  4. customcompletion of the reaction
  5. customthe cooled reaction mixture
  6. extractionextracted with EtOAc (3×40 mL)
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-abea978d5dd643319252579dd7c70a47
Source dataset
uspto-grants-2016_04
Patent number
US09321774B2

Reaction notes

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