1-Pentyne → HCID 67436425, compound

HRID 1968894Notes

Reaction equation

HRID 1968894 reaction equation
[C:1]([O:5][C:6](=[O:34])[NH:7][C@H:8]([CH2:13][N:14]([C:27]1[CH:32]=[CH:31][C:30](Br)=[CH:29][CH:28]=1)[C:15]([C@@H:17]1[CH2:19][C@H:18]1[C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[N:21]=1)=[O:16])[C@@H:9]([CH3:12])[CH2:10][CH3:11])([CH3:4])([CH3:3])[CH3:2].[CH:35]#[C:36][CH2:37][CH2:38][CH3:39].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:1]([O:5][C:6](=[O:34])[NH:7][C@H:8]([CH2:13][N:14]([C:15]([C@H:17]1[CH2:19][C@@H:18]1[C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[N:21]=1)=[O:16])[C:27]1[CH:32]=[CH:31][C:30]([C:35]#[C:36][CH2:37][CH2:38][CH3:39])=[CH:29][CH:28]=1)[C@@H:9]([CH3:12])[CH2:10][CH3:11])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 123091-PentyneHCID 2724141Tetrabutylammonium FluorideHCID 67437196HCID 67437196, compound

Product 1

HCID 67436425HCID 67436425, compoundYield 99.6%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
90 °C

Procedure

[(1S,2S)-1-({(4-Bromo-phenyl)-[trans-2-(6-fluoro-pyridin-2-yl)-cyclopropanecarbonyl]-amino}-methyl)-2-methyl-butyl]-carbamic acid t-butyl ester (0.068 g, 0.127 mmol), 1-pentyne (0.05 mL, 0.509 mmol), PdCl2(PPh3)2 (0.017 g, 0.025 mmol) and 1N TBAF in THF (0.76 mL, 0.762 mmol) were mixed in THF (1 mL) in sealed microwave flask. The reaction mixture was heated at 90° C. at normal setting for 30 minutes. The reaction mixture was quenched with brine. The aqueous phase was extracted by ethyl acetate (3×7 mL). The combined organic layers were washed brine and dried over MgSO4, filtered and concentrated to give yellow oil. The crude product was purified via column chromatography on silica gel with a gradient of 0%-50% of ethyl acetate in hexanes to afford the title product as yellow oil (0.066 g, 99% yield): 1H NMR (400 MHz, CDCl3) δ ppm 7.32 (m, 4H), 6.86 (m, 3H), 6.42 (m, 1H), 4.76 (d, J=9.1 Hz, 1H), 4.11 (m, 1H), 3.48 (m, 1H), 2.95 (td, J=13.1, 3.8 Hz, 1H), 2.42 (m, 1H), 2.16 (td, J=7.0, 3.4 Hz, 2H), 1.67 (m, 1H), 1.40 (m, 4H), 1.22 (m, 11H), 0.84 (m, 3H), 0.63 (m, 6H); LCMS (ESI) m/e 522.4 [(M+H), calcd for C31H41FN3O3 522.7].

Workup

  1. customThe reaction mixture was quenched with brine
  2. extractionThe aqueous phase was extracted by ethyl acetate (3×7 mL)
  3. washThe combined organic layers were washed brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give yellow oil
  8. customThe crude product was purified via column chromatography on silica gel with a gradient of 0%-50% of ethyl acetate in hexanes

Sources & evidence

ORD record
ord-6265c89296e548d5b9ad2a27b0f9a1e1
Source dataset
uspto-grants-2013_04
Patent number
US08426414B2

Reaction notes

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