Ethyl propiolate → HCID 67111289, compound

HRID 540783Notes

Reaction equation

HRID 540783 reaction equation
[C:1]([O:5][CH2:6][CH3:7])(=[O:4])[C:2]#[CH:3].[Li]CCCC.[C:13]([NH:20][CH:21]1[CH2:29][C:28]2[C:23](=[CH:24][CH:25]=[C:26](I)[CH:27]=2)[CH2:22]1)([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14]>C1COCC1.C(Cl)Cl.[Cl-].[Zn+2].[Cl-].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:16]([O:15][C:13]([NH:20][CH:21]1[CH2:29][C:28]2[C:23](=[CH:24][CH:25]=[C:26]([C:3]#[C:2][C:1]([O:5][CH2:6][CH3:7])=[O:4])[CH:27]=2)[CH2:22]1)=[O:14])([CH3:19])([CH3:17])[CH3:18]

Participants

8

Reactant 3

HCID 12182Ethyl propiolateHCID 67111290HCID 67111290, compoundHCID 178418339Butyllithium

Product 1

HCID 67111289HCID 67111289, compoundYield 54%

Reagents, catalysts & solvents 4

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent4×

Procedure

A mixture of ethyl propiolate (0.85 mL, 8.36 mmol) in THF (20 mL) was treated with a 2.5 M solution of n-BuLi in THF (3.3 mL, 8.3 mmol) at −78° C., stirred for 10 min, followed by addition of a 1.0 M solution of zinc chloride in THF (8.4 mL, 8.4 mmol). Warmed reaction to RT, added a solution of N-Boc-2-amino-5-iodo-2,3-dihydro-1H-indene (0.800 g, 2.22 mmol) in THF (1 mL) followed by Pd(PPh3)4 (0.30 g, 0.26 mmol). Warmed reaction mixture to 60° C., stirred for 2 hours, then cooled. Diluted with DCM, washed with 1 N HCl, water, dried (Na2SO4), conc. Chromatography on SiO2 (0-50% EtOAc/hexanes) gave the intermediate ethyl 3-{2-[(tert-butoxycarbonyl)amino]-2,3-dihydro-1H-inden-5-yl}prop-2-ynoate (392 mg, 54% yield): 1H NMR (600 MHz, CDCl3) δ 7.41 (s, 1H), 7.39 (d, J=8.5 Hz, 1H), 7.19 (d, J=7.6 Hz, 1H), 4.71 (br s, 1H), 4.45 (br s, 1H), 4.27 (q, J=7.0 Hz, 2H), 3.23-3.28 (m, 2H), 2.75-2.81 (m, 2H), 1.42 (s, 9H), 1.33 (t, J=Hz, 3H); MS cal'd for C19H23NO4Na [M+Na]+352.2. found 352.1.

Workup

  1. temperatureWarmed
  2. customreaction to RT
  3. temperatureWarmed
  4. customreaction mixture to 60° C.
  5. stirringstirred for 2 hours
  6. temperaturecooled
  7. washwashed with 1 N HCl, water
  8. dry with materialdried (Na2SO4), conc. Chromatography on SiO2 (0-50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-58b143afa67f434c999d9ebdc9945fc0
Source dataset
uspto-grants-2014_10
Patent number
US08871796B2

Reaction notes

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