Phthalimide → [2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-2-phenyl-ethyl]-carbamic acid tert-butyl ester

HRID 1186500Notes

Reaction equation

HRID 1186500 reaction equation
[C:1]([O:5][C:6](=[O:17])[NH:7][CH2:8][CH:9](O)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2].[C:18]1(=[O:28])[NH:22][C:21](=[O:23])[C:20]2=[CH:24][CH:25]=[CH:26][CH:27]=[C:19]12.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(/N=N/C(OCC)=O)=O>>[C:1]([O:5][C:6](=[O:17])[NH:7][CH2:8][CH:9]([N:22]1[C:18](=[O:28])[C:19]2[C:20](=[CH:24][CH:25]=[CH:26][CH:27]=2)[C:21]1=[O:23])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 4

HCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 9816137tert-butyl N-(2-hydroxy-2-phenylethyl)carbamate

Product 1

HCID 57826431[2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-2-phenyl-ethyl]-carbamic acid tert-butyl ester

Conditions

Temperature
0 °C

Procedure

To a solution of (2-hydroxy-2-phenyl-ethyl)-carbamic acid tert-butyl ester (34.4 g, 145.0 mmol), phthalimide (21.3 g, 145 mmol), and PPh3 (49.4 g, 188.5 mmol) was added drop-wise DEAD (32.8 g, 188.5 mmol) under stirring at 0° C. After addition, the mixture was stirred at room temperature for an additional 1 hour. The mixture was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (petroleum ether:ethyl acetate, 20:1 to 5:1) to give [2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-2-phenyl-ethyl]-carbamic acid tert-butyl ester as a white solid. (Yield 39 g, 74%) 1H NMR (300 MHz, CDCl3): δ 7.88-7.80 (m, 2H), 7.74-7.68 (m, 2H), 7.49-7.47 (m, 2H), 7.38-7.26 (m, 3H), 5.56-5.50 (m, 1H), 4.83 (brs, 1H), 4.28-4.22 (m, 1H), 3.93-3.87 (m, 1H), 1.35 (s, 9H). LC-MS: [M-Boc+H]+ 267.

Workup

  1. additionAfter addition
  2. stirringthe mixture was stirred at room temperature for an additional 1 hour
  3. concentrationThe mixture was concentrated under reduced pressure
  4. customThe residue was purified by column chromatography on silica gel (petroleum ether:ethyl acetate, 20:1 to 5:1)

Sources & evidence

ORD record
ord-746adf0ab2c5430389a6736b60968c3f
Source dataset
uspto-grants-2014_03
Patent number
US08673905B2

Reaction notes

Loading…