1-methyl-2-(tributylstannyl)-1H-pyrrole → 2-amino-5-(1-methyl-1H-pyrrol-2-yl)-4-trifluoromethyl-benzoic acid methyl ester

HRID 906553Notes

Reaction equation

HRID 906553 reaction equation
[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[C:8](I)[C:7]([C:11]([F:14])([F:13])[F:12])=[CH:6][C:5]=1[NH2:15].[CH3:17][N:18]1[CH:22]=[CH:21][CH:20]=[C:19]1[Sn](CCCC)(CCCC)CCCC>O1CCOCC1>[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[C:8]([C:19]2[N:18]([CH3:17])[CH:22]=[CH:21][CH:20]=2)[C:7]([C:11]([F:14])([F:13])[F:12])=[CH:6][C:5]=1[NH2:15]

Participants

4

Reactant 2

HCID 27693971-methyl-2-(tributylstannyl)-1H-pyrrole2×HCID 53436880Methyl 2-amino-5-iodo-4-(trifluoromethyl)benzoate

Product 1

HCID 591645032-amino-5-(1-methyl-1H-pyrrol-2-yl)-4-trifluoromethyl-benzoic acid methyl esterYield 14.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

2-Amino-5-iodo-4-trifluoromethyl-benzoic acid methyl ester (400 mg, 1.16 mmol) and 1-methyl-2-tributylstannanyl-1H-pyrrole (643 mg, 1.5 equiv) were weighed in air and added in a flame-dried flask. [Bistriphenylphosphine]dichloropalladium (124.5 mg, 0.15 equiv) was added and the flask was closed by a septum. Dioxane (16 mL) was added and the mixture was stirred for 1 h (TLC control) at 100° C. After 1 h, 1-methyl-2-tributylstannyl-1H-pyrrole (429 mg, 1 equiv) was added and the mixture was stirred for 35 h (TLC control) at 100° C. The solvent was removed in vacuo, the residue was taken in DCM and washed with a saturated solution of NaHCO3, water and brine. The organic phase was dried over Na2SO4 and evaporated to dryness. The crude product was purified by flash chromatography (hexanes to EtOAc/hexanes (4:6)) to furnish 2-amino-5-(1-methyl-1H-pyrrol-2-yl)-4-trifluoromethyl-benzoic acid methyl ester (50 mg, 14.5%) as a yellow oil. ESI-MS: m/z 299 [M+H]+, rt 5.78 min.

Workup

  1. additionadded in a flame-dried flask
  2. customthe flask was closed by a septum
  3. waitAfter 1 h
  4. stirringthe mixture was stirred for 35 h (TLC control) at 100° C
  5. customThe solvent was removed in vacuo
  6. washwashed with a saturated solution of NaHCO3, water and brine
  7. dry with materialThe organic phase was dried over Na2SO4
  8. customevaporated to dryness
  9. customThe crude product was purified by flash chromatography (hexanes to EtOAc/hexanes (4:6))

Sources & evidence

ORD record
ord-26f5578606644dd0a5f68f9623890f24
Source dataset
uspto-grants-2011_09
Patent number
US08012988B2

Reaction notes

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