Acetic Acid → {Benzyloxycarbonyl-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-ylamino)-ethyl]-amino}-acetic acid ethyl ester

HRID 2381922Notes

Reaction equation

HRID 2381922 reaction equation
[CH2:1]([O:3][C:4](=[O:31])[CH2:5][N:6]([C:21]([O:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:22])[CH2:7]/[CH:8]=[N:9]/[N:10]1[C:18](=[O:19])[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]1=[O:20])[CH3:2].C([BH3-])#N.[Na+].C(O)(=O)C>CC#N.CCOC(C)=O>[CH2:1]([O:3][C:4](=[O:31])[CH2:5][N:6]([C:21]([O:23][CH2:24][C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1)=[O:22])[CH2:7][CH2:8][NH:9][N:10]1[C:18](=[O:19])[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]1=[O:20])[CH3:2]

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 87496342ethyl 2-[[(2E)-2-(1,3-dioxoisoindol-2-yl)iminoethyl]-phenylmethoxycarbonylamino]acetate

Product 1

HCID 68557343{Benzyloxycarbonyl-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-ylamino)-ethyl]-amino}-acetic acid ethyl esterYield 81.2%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (benzyloxycarbonyl-{2-[(E)-1,3-dioxo-1,3-dihydro-isoindol-2-ylimino]ethyl}-amino)-acetic acid ethyl ester (7.7 mmol) in CH3CN (65 mL) is treated with sodium cyanoborohydride (1.92 g, 30.5 mmol), and acetic acid (6.8 mL, 118.8 mmol) is added with stirring under N2. After 5.5 h, the reaction solution is diluted with EtOAc (150 mL) and washed with saturated aqueous KHCO3 (3×50 mL) and saturated aqueous NaCl (50 mL). The organic phase is dried (MgSO4), filtered, and concentrated in vacuo. The residue is purified by silica gel chromatography (75:25 to 50:50 heptane:ethyl acetate gradient elution) to afford {benzyloxycarbonyl-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-ylamino)-ethyl]-amino}-acetic acid ethyl ester as an oil (2.66 g, 81%). MS: 426 (M+H); 1H NMR (300 MHz, CDCl3) δ 7.79-7.91 (m, 2H), 7.69-7.79 (m, 2H), 7.17-7.39 (m, 5H), 5.04-5.21 (m, 2H), 4.87-5.04 (m, 1H), 4.04-4.23 (m, 4H), 3.48-3.59 (m, 2H), 3.18-3.38 (m, 2H), 1.10-1.30 (m, 3H).

Workup

  1. additionis added
  2. washwashed with saturated aqueous KHCO3 (3×50 mL) and saturated aqueous NaCl (50 mL)
  3. dry with materialThe organic phase is dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue is purified by silica gel chromatography (75:25 to 50:50 heptane:ethyl acetate gradient elution)

Sources & evidence

ORD record
ord-110ae9cb1f6243f985e93cca7577e535
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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