Trifluoroacetic acid → (2R)-amino-5-(1,3-dioxo-1,3-dihydroisoindol-2-yl)pentanoic acid t-butyl ester

HRID 651318Notes

Reaction equation

HRID 651318 reaction equation
[C:1]([O:5][C:6](=[O:30])[C@H:7]([NH:22]C(OC(C)(C)C)=O)[CH2:8][CH2:9][CH2:10][N:11]1[C:19](=[O:20])[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:12]1=[O:21])([CH3:4])([CH3:3])[CH3:2].FC(F)(F)C(O)=O>ClCCl>[C:1]([O:5][C:6](=[O:30])[C@H:7]([NH2:22])[CH2:8][CH2:9][CH2:10][N:11]1[C:12](=[O:21])[C:13]2[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:19]1=[O:20])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 15549668(2R)-(t-butyloxycarbonylamino)-5-(1,3-dioxo-1,3-dihydroisoindol-2-yl)pentanoic acid t-butyl ester

Product 1

HCID 15549669(2R)-amino-5-(1,3-dioxo-1,3-dihydroisoindol-2-yl)pentanoic acid t-butyl esterYield 70.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of the title G compound, (2R)-(t-butyloxycarbonylamino)-5-(1,3-dioxo-1,3-dihydroisoindol-2-yl)pentanoic acid t-butyl ester (4.83 g, 11.55 mmol) in 18 mL of dichloromethane is treated with trifluoroacetic acid (TFA; 6.00 mL, 78 mmol) at 0° C. After stirring for 1 h at this temperature, the solution is concentrated under reduced pressure without heating, and the residue is partitioned between 100 mL of ethyl acetate and 50 mL of 1M aqueous NaHCO3. The organic phase is dried over anhydrous Na2SO4 and concentrated. Chomatography on silica gel (eluant; 1/1—ethyl acetate/hexane) affords 2.58 g (70%) of (2R)-amino-5-(1,3-dioxo-1,3-dihydroisoindol-2-yl)pentanoic acid t-butyl ester as a colorless foam: NMR(CDCl3) 1.46 (s, 9H), 1.80-2.06 (m, 4H), 3.73 (t, 2H, J=6.2), 3.97 (t, 1H, J=6.3), 7.68-7.71 (m, 2H), 7.82-7.85 (m, 2H).

Workup

  1. concentrationthe solution is concentrated under reduced pressure
  2. temperaturewithout heating
  3. customthe residue is partitioned between 100 mL of ethyl acetate and 50 mL of 1M aqueous NaHCO3
  4. dry with materialThe organic phase is dried over anhydrous Na2SO4
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-d5108836bb1a46bc8a16daec1a8ae216
Source dataset
uspto-grants-2001_08
Patent number
US06277987B1

Reaction notes

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