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

HRID 1696834Notes

Reaction equation

HRID 1696834 reaction equation
[CH2:1]([O:8][C:9](=[O:37])[NH:10][CH2:11][CH2:12][C:13]#[C:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]#[C:22][CH2:23][CH:24]([N:26]2[C:34](=[O:35])[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:27]2=[O:36])[CH3:25])=[CH:17][CH:16]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H][H].CCN(CC)CC.C(Cl)(OCC1C=CC=CC=1)=O>C1COCC1.[Pd]>[CH2:1]([O:8][C:9](=[O:37])[NH:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18]([CH2:21][CH2:22][CH2:23][CH:24]([N:26]2[C:27](=[O:36])[C:28]3[C:33](=[CH:32][CH:31]=[CH:30][CH:29]=3)[C:34]2=[O:35])[CH3:25])=[CH:17][CH:16]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 10387Benzyl chloroformate2×HCID 66860631(4-{4-[4-(1,3-Dioxo-1,3-dihydroisoindol-2-yl)pent-1-ynyl]phenyl}but-3-ynyl)-carbamic acid benzyl esterHCID 178418361HCID 178418361, compound

Product 1

HCID 66860569(4-{4-[4-(1,3-Dioxo-1,3-dihydroisoindol-2-yl)pentyl]phenyl}butyl)carbamic acid benzyl esterYield 35%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A solution containing compound 24 (2.53 g, 5.15 mmol) dissolved in THF (100 mL) was vacuumed and refilled with nitrogen. The procedure was repeated five times. To the solution was added palladium catalyst (0.5 g, 10% Pd on carbon, 50% wet). The flask was then pressurized with hydrogen gas to 45 psi. The mixture was then shaken overnight at room temperature. The catalyst was filtered under vacuum and washed with ethanol (3×20 mL). The filtrate and washings were combined and concentrated under vacuum. The residue was taken into dichloromethane (25 mL). To the newly formed solution was added Et3N (2.32 mL, 15.45 mmol). The solution was then cooled to 0° C. in an ice bath. CbzCl (1.32 g, 7.730 mmol) was added dropwise over 10 min to the solution, which, after the addition of CbzCl, was allowed to slowly warm to ambient temperature over 3 h and continuously stirred overnight. The reaction was quenched with water (30 mL). Two layers were separated. The organic layer was washed with brine (3×30 mL), dried over anhydrous Na2SO4, and concentrated. The resulting residue was subjected to column chromatography eluting with 0-30% ethyl acetate in hexanes to afford the desired product 25 (0.90 g, 35%) as a colorless, viscous oil: 1H NMR (300 MHz, CDCl3) δ 1.45 (d, 3H), 1.45-1.66 m, 6H), 1.72-1.86 (m, 2H), 2.06-2.16 (m, 2H), 2.55 (m, 4H), 3.20 (m, 2H), 4.38 (m, 1H), 4.80 (br, 1H), 5.08 (s, 2H), 7.04 (s, 4H), 7.34 (m, 5H), 7.69 (dd, 2H), 7.81 (dd, 1H); m/z (ESI) 499 [C31H34N2O4+H]+.

Workup

  1. additionrefilled with nitrogen
  2. filtrationThe catalyst was filtered under vacuum
  3. washwashed with ethanol (3×20 mL)
  4. concentrationconcentrated under vacuum
  5. temperatureThe solution was then cooled to 0° C. in an ice bath
  6. temperatureto slowly warm to ambient temperature over 3 h and continuously stirred overnight
  7. customThe reaction was quenched with water (30 mL)
  8. customTwo layers were separated
  9. washThe organic layer was washed with brine (3×30 mL)
  10. dry with materialdried over anhydrous Na2SO4
  11. concentrationconcentrated
  12. washeluting with 0-30% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-ca9550d521494ccd87a57bed5ea17ba7
Source dataset
uspto-grants-2012_04
Patent number
US08163758B2

Reaction notes

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