Ammonium Chloride → HCID 59180075, compound

HRID 601826Notes

Reaction equation

HRID 601826 reaction equation
C[Si]([C:5]#[C:6][C:7]1[CH:8]=[C:9]([CH:30]=[CH:31][CH:32]=1)[CH2:10][CH:11]1[C:18]2[CH:17]=[C:16]([C:19]([O:21][CH3:22])=[O:20])[N:15](C(OC(C)(C)C)=O)[C:14]=2[CH2:13][CH2:12]1)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Cl-].[NH4+]>C1COCC1.FC(F)(F)C(O)=O>[C:6]([C:7]1[CH:8]=[C:9]([CH:30]=[CH:31][CH:32]=1)[CH2:10][CH:11]1[C:18]2[CH:17]=[C:16]([C:19]([O:21][CH3:22])=[O:20])[NH:15][C:14]=2[CH2:13][CH2:12]1)#[CH:5]

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 2724141Tetrabutylammonium FluorideHCID 66873381HCID 66873381, compound

Product 1

HCID 59180075HCID 59180075, compound

Reagents, catalysts & solvents 2

HCID 6422Trifluoroacetic acidCatalystHCID 8028TetrahydrofuranSolvent

Procedure

The title compound was synthesized in two steps. First, BOC protected methyl 4-(3-bromobenzyl)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate (1-tert-butyl 2-methyl 4-(3-bromobenzyl)-5,6-dihydrocyclopenta[b]pyrrole-1,2(4H)-dicarboxylate) (0.101 g, 0.23 mmol) was coupled with ethynyltrimethylsilane (0.065 mL, 0.46 mmol) according to General Procedure 9.4 to give 1-tert-butyl 2-methyl 4-(3-((trimethylsilyl)ethynyl)benzyl)-5,6-dihydrocyclopenta[b]pyrrole-1,2(4H)-dicarboxylate. The trimethylsilyl group and BOC group were then removed. 1-tert-butyl 2-methyl 4-(3-((trimethylsilyl)ethynyl)benzyl)-5,6-dihydrocyclopenta[b]pyrrole-1,2(4H)-dicarboxylate (0.061 g, 0.135 mmol) was dissolved in anhydrous THF (2 mL), and tetrabutylammoniumfluoride (0.68 mL of 1 M solution in THF, 0.68 mmol) was added, and the reaction was stirred at ambient temperature for 5 min. The reaction was heated to 60° C. and stirred for 3 h, after which 2 drops of trifluoroacetic acid was added. The reaction was stirred at 60° C. for 18 h; then allowed to cool to ambient temperature. Aqueous ammonium chloride was added and the product extracted two times with ethyl acetate. The organic layer was dried over Na2SO4, concentrated and purified by column chromatography (Isco CombiFlash) eluting with a gradient of 0-20% EtOAc/heptane to afford both the title compound (methyl 4-(3-ethynylbenzyl)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate) as well as N-BOC product (1-tert-butyl 2-methyl 4-(3-ethynylbenzyl)-5,6-dihydrocyclopenta[b]pyrrole-1,2(4H)-dicarboxylate). (0.014 g and 0.016 g, respectively). 1H NMR (400 MHz, ACETONE-d6) δ ppm 2.06-2.14 (m, 1H) 2.47-2.58 (m, 1H) 2.58-2.74 (m, 2H) 2.80 (d, J=7.42 Hz, 2H) 3.25-3.33 (m, 1H) 3.60 (s, 1H) 3.71 (s, 3H) 6.27-6.30 (m, 1H) 7.23-7.39 (m, 4H) 10.48 (br. s, 1H).

Workup

  1. customThe trimethylsilyl group and BOC group were then removed
  2. temperatureThe reaction was heated to 60° C.
  3. stirringstirred for 3 h
  4. stirringThe reaction was stirred at 60° C. for 18 h
  5. temperatureto cool to ambient temperature
  6. extractionthe product extracted two times with ethyl acetate
  7. dry with materialThe organic layer was dried over Na2SO4
  8. concentrationconcentrated
  9. custompurified by column chromatography (Isco CombiFlash)
  10. washeluting with a gradient of 0-20% EtOAc/heptane

Sources & evidence

ORD record
ord-c3ccb6583d394b3aa11cb054d5d08308
Source dataset
uspto-grants-2011_03
Patent number
US07902252B2

Reaction notes

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