Triethylamine → (4-{4-[4-(1,3-Dioxo-1,3-dihydroisoindol-2-yl)pent-1-ynyl]phenyl}but-3-ynyl)-carbamic acid benzyl ester

HRID 1696833Notes

Reaction equation

HRID 1696833 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.CCN(CC)CC.[CH3:30][CH:31]([N:35]1[C:43](=[O:44])[C:42]2[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=2)[C:36]1=[O:45])[CH2:32][C:33]#[CH:34]>C1COCC1.[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>[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]([C:34]#[C:33][CH2:32][CH:31]([N:35]2[C:36](=[O:45])[C:37]3[C:42](=[CH:41][CH:40]=[CH:39][CH:38]=3)[C:43]2=[O:44])[CH3:30])=[CH:17][CH:16]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 113333492-(1-Methylbut-3-ynyl)isoindole-1,3-dioneHCID 59750570Benzyl [4-(4-iodophenyl)but-3-yn-1-yl]carbamate

Product 1

HCID 66860631(4-{4-[4-(1,3-Dioxo-1,3-dihydroisoindol-2-yl)pent-1-ynyl]phenyl}but-3-ynyl)-carbamic acid benzyl esterYield 92.2%

Reagents, catalysts & solvents 3

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

Procedure

A 100 mL, round-bottom flask containing a mixture of [4-(4-iodophenyl)but-3-ynyl]carbamic acid benzyl ester 23 (2.33 g, 5.75 mmol), CuI (0.22 g, 1.15 mmol), Et3N (10 mL) and THF (anhydrous, 15 mL) was vacuumed and refilled with nitrogen. The procedure was repeated three more time. To the suspension was added Pd(PPh3)2Cl2 (0.40 g, 0.58 mmol) in one portion, followed by a solution of compound 22 (1.35 g, 6.32 mmol) dissolved in THF (anhydrous, 10 mL), which was added dropwise over 2 h. The stirring was continued overnight. The reaction mixture was concentrated under vacuum. The residue was subjected to column chromatography eluting with a mixture of ethyl acetate (0-25%) and hexanes to afford the desired product 24 (2.60 g, 92%) as an off-yellow solid. 1H NMR (500 MHz, CDCl3) δ 1.71 (d, 3H), 2.61 (t, 2H), 2.92 (m, 1H), 3.14 (m, 1H), 3.43 (t, 2H), 4.67 (m, 1H), 5.07 (br, 1H), 5.11 (s, 2H), 7.12-7.33 (m, 9H), 7.71 (dd, 2H), 7.92 (dd, 1H); m/z (ESI) 491 [C31H26N2O4+H]+.

Workup

  1. additionA 100 mL, round-bottom flask containing
  2. additionrefilled with nitrogen
  3. additionwhich was added dropwise over 2 h
  4. concentrationThe reaction mixture was concentrated under vacuum
  5. washeluting with a mixture of ethyl acetate (0-25%) and hexanes

Sources & evidence

ORD record
ord-5eaf1a7273ed4f45937882eeae77692a
Source dataset
uspto-grants-2012_04
Patent number
US08163758B2

Reaction notes

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