Methyl 2-[(tert-butoxycarbonyl)amino]pent-4-ynoate → HCID 59750578, compound

HRID 1175711Notes

Reaction equation

HRID 1175711 reaction equation
[CH2:1]([O:8][C:9](=[O:22])[NH:10][CH2:11][CH2:12][C:13]#[C:14][C:15]1[CH:20]=[CH:19][C:18](I)=[CH:17][CH:16]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:23][O:24][C:25](=[O:38])[C@H:26]([NH:30][C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27][C:28]#[CH:29].COC(=O)C(NC(OC(C)(C)C)=O)CC#C>C1COCC1.C(N(CC)CC)C.[Cu]I.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>[CH3:23][O:24][C:25](=[O:38])[C@H:26]([NH:30][C:31]([O:33][C:34]([CH3:36])([CH3:35])[CH3:37])=[O:32])[CH2:27][C:28]#[C:29][C:18]1[CH:19]=[CH:20][C:15]([C:14]#[C:13][CH2:12][CH2:11][NH:10][C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[O:22])=[CH:16][CH:17]=1

Participants

8

Reactant 3

HCID 10537281Methyl 2-[(tert-butoxycarbonyl)amino]pent-4-ynoateHCID 12149490(R)-2-(Boc-amino)-4-pentynoic acid methyl esterHCID 59750570Benzyl [4-(4-iodophenyl)but-3-yn-1-yl]carbamate2×

Product 1

HCID 59750578HCID 59750578, compoundYield 99%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolvent

Procedure

Compound 22, [4-(4-iodophenyl)-but-3-ynyl]carbamic acid benzyl ester (0.52 g, 1.283 mmol) was dissolved in a mixture of anhydrous THF and triethylamine (8 mL, 1/1, v/v). To the solution was added copper (I) iodide (0.025 g, 0.128 mmol). The mixture was stirred at room temperature for 15 min. The flask was then evacuated and re-filled with Argon. The procedure was repeated three more times to ensure no oxygen remained. The catalyst, dichlorobis(triphenylphosphine)palladium(II) (0.09 g, 0.128 mmol) was added into the mixture under Argon protection. The mixture was further stirred at room temperature for 30 min. The other starting material 23, 2-tert-butoxycarbonylamino-pent-4-ynoic acid methyl ester (0.32 g, 1.412 mmol), dissolved in THF (4 mL) was added dropwise over 15 min. The newly formed reaction mixture was further stirred overnight at room temperature. The solid in the reaction mixture was vacuum filtered. The filtrate was concentrated. The residue was re-dissolved in dichloromethane and purified by column chromatography, eluting with a mixture of ethyl acetate (0-25%) and hexanes (100-75%) to afford the product 24 (0.64 g, 99%) as a gummy, yellowish solid. 1H NMR (300 MHz, CDCl3): δ 1.46 (s, 9H), 2.64 (t, J=6.3 Hz, 2H), 2.95 (t, J=4.1 Hz, 2H), 3.42 (m, 2H), 3.79 (s, 3H), 4.56 (m, 1H), 5.12 (s, 2H), 5.38 (br s, 1H), 7.29 (s, 4H), 7.35 (m, 5H). m/z (APCI) 502 [C29H32N2O6—H]+.

Workup

  1. customThe flask was then evacuated
  2. additionre-filled with Argon
  3. stirringThe mixture was further stirred at room temperature for 30 min
  4. additionwas added dropwise over 15 min
  5. customThe newly formed reaction mixture
  6. stirringwas further stirred overnight at room temperature
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated
  9. dissolutionThe residue was re-dissolved in dichloromethane
  10. custompurified by column chromatography
  11. washeluting with a mixture of ethyl acetate (0-25%) and hexanes (100-75%)

Sources & evidence

ORD record
ord-bcc381248d494d13a61d2c150bb5476b
Source dataset
uspto-grants-2010_11
Patent number
US07842697B2

Reaction notes

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