Tris(hydroxymethyl)aminomethane → HCID 57435084, compound

HRID 1366895Notes

Reaction equation

HRID 1366895 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[NH:7][CH:8]=[CH:9][CH:10]=1)=[O:5])[CH3:2].[Cl-].[Al+3].[Cl-].[Cl-].[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][C:23](Cl)=[O:24])=[CH:18][CH:17]=1.C(O)C(N)(CO)CO>ClC(Cl)C>[CH2:1]([O:3][C:4]([C:6]1[NH:7][CH:8]=[C:9]([C:23](=[O:24])[CH2:22][C:19]2[CH:20]=[CH:21][C:16]([Cl:15])=[CH:17][CH:18]=2)[CH:10]=1)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 6503Tris(hydroxymethyl)aminomethaneHCID 906924-Chlorophenylacetyl chlorideHCID 255670Ethyl 1H-pyrrole-2-carboxylateHCID 6451240Aluminum(III) Chloride

Product 1

HCID 57435084HCID 57435084, compoundYield 48.4%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent3×

Conditions

Temperature
60 °C

Procedure

Ethylpyrrole-2-carboxylate (1.0195 g, 7.33 mmol) in a minimal amount of dichloroethane was added to an ice cooled stirring mixture of aluminum chloride (1.934 g, 14.5 mmol) and 4-chlorobenzeneacetyl chloride (2.7841 g, 14.73 mmol) in dichloroethane (10.9 mL, 0.67 M) under N2. After stirring 10 min, the ice bath was removed, and the reaction was stirred at room temperature for 60 minutes, with little change by TLC (9:1 Hexanes:EtOAc): After heating to 60° C. for an additional hour, only a small quantity of starting material was left by TLC. The reaction was cooled to room temperature, PS-Trisamine™ resin (6.3954 g, 24.30 mmol) and dichloroethane (10 mL) were added, and the reaction was stirred for 3 hours. The reaction was then filtered through a glass-fritted funnel directly into ice water. The resin was rinsed with CH2Cl2, then the organic layers were removed, dried with Na2SO4, filtered, concentrated, and purified by silica gel chromatography (Combiflash column, 95:5 to 50:50 Hexanes:EtOAc) to obtain 1.0345 g (48.4%) 37 as a pale orange solid. Note: A small amount of CH2Cl2 was required to solubilize the crude product before placement on the silica column. 1H (CDCl3, 400 MHz): δ 10.07 (1H, broad s), 7.55-7.52 (1H, m), 7.33-7.30 (1H, m), 7.27 (2H, d, J=8.3 Hz), 7.14 (2H, d, J=8.3 Hz), 4.35 (2H, q, J=7.0 Hz), 4.04 (2H, s), 1.37 (3H, t, J=7.1 Hz) ppm. 13C (CDCl3, 100 MHz): δ 192.55, 160.97, 133.10, 132.75, 130.76, 128.69, 126.80, 126.25, 124.30, 114.95, 61.06, 45.79, 14.31 ppm. DEPT (CDCl3, 100 MHz): CH3 carbons: 14.31; CH2 carbons: 61.06, 45.79; CH carbons: 130.76, 128.69, 126.80, 114.96 ppm. HPLC: 10.049 min.

Workup

  1. temperaturecooled
  2. stirringAfter stirring 10 min
  3. customthe ice bath was removed
  4. stirringthe reaction was stirred at room temperature for 60 minutes, with little change by TLC (9:1 Hexanes:EtOAc)
  5. waitonly a small quantity of starting material was left by TLC
  6. temperatureThe reaction was cooled to room temperature
  7. stirringthe reaction was stirred for 3 hours
  8. filtrationThe reaction was then filtered through a glass-fritted funnel directly into ice water
  9. washThe resin was rinsed with CH2Cl2
  10. customthe organic layers were removed
  11. dry with materialdried with Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. custompurified by silica gel chromatography (Combiflash column, 95:5 to 50:50 Hexanes:EtOAc)

Sources & evidence

ORD record
ord-fc68e889dece4e55846da0ed2ea61a9f
Source dataset
uspto-grants-2011_02
Patent number
US07893098B2

Reaction notes

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