Phthalimide → (S)-tert-butyl (2-(3-chlorophenyl)-2-(1,3-dioxoisoindolin-2-yl)ethyl)carbamate

HRID 595803Notes

Reaction equation

HRID 595803 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8](O)[CH2:9][NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH:5]=[CH:6][CH:7]=1.[C:19]1(=[O:29])[NH:23][C:22](=[O:24])[C:21]2=[CH:25][CH:26]=[CH:27][CH:28]=[C:20]12.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C@H:8]([N:23]2[C:19](=[O:29])[C:20]3[C:21](=[CH:25][CH:26]=[CH:27][CH:28]=3)[C:22]2=[O:24])[CH2:9][NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 99645701(R)-tert-butyl (2-(3-chlorophenyl)-2-hydroxyethyl)carbamate

Product 1

HCID 118054581(S)-tert-butyl (2-(3-chlorophenyl)-2-(1,3-dioxoisoindolin-2-yl)ethyl)carbamateYield 58.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of (R)-tert-butyl (2-(3-chlorophenyl)-2-hydroxyethyl)carbamate (8.12 g, 29.9 mmol) in THF (100 mL) was added phthalimide (6.16 g, 41.8 mmol) and polymer-bound triphenylphosphine (3 mmol of PPh3/1 g of resin, 9.8 g). DTBAD (7.09 g, 30.8 mmol) in THF (20 mL) was added slowly at room temperature to the reaction mixture, which was then stirred at room temperature overnight. The reaction mixture was filtered through Celite and washed with EtOAc. The resulting filtrate was washed with Na2CO3 solution, water and brine, dried over anhydrous sodium sulfate, filtered off, and concentrated in vacuo. The crude material was purified by flash chromatography (0-30% EtOAc/heptane) yielding (S)-tert-butyl (2-(3-chlorophenyl)-2-(1,3-dioxoisoindolin-2-yl)ethyl)carbamate (58.4%). LCMS (m/z): 301.1 (MH+-Boc), 1.06 min.

Workup

  1. filtrationThe reaction mixture was filtered through Celite
  2. washwashed with EtOAc
  3. washThe resulting filtrate was washed with Na2CO3 solution, water and brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered off
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified by flash chromatography (0-30% EtOAc/heptane)

Sources & evidence

ORD record
ord-103ed46c889045198061c41e964cc5e9
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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