(4S)-5-(Benzyloxy)-4-(((benzyloxy)carbonyl)amino)-5-oxopentanoic acid → (2S)-2 Benzyloxycarbonylamino-5-oxo-heptanedioic acid 1-benzyl ester 7-ethyl ester

HRID 215698Notes

Reaction equation

HRID 215698 reaction equation
[CH:1]1[CH:6]=[CH:5][C:4]([CH2:7][O:8][C:9]([C@@H:11]([NH:17][C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:19])[CH2:12][CH2:13][C:14]([OH:16])=O)=[O:10])=[CH:3][CH:2]=1.C([O-])(=O)[CH2:29][C:30]([O-:32])=[O:31].[CH2:35]([Mg+2])[CH3:36]>C1COCC1>[CH2:35]([O:32][C:30](=[O:31])[CH2:29][C:14](=[O:16])[CH2:13][CH2:12][C@H:11]([NH:17][C:18]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19])[C:9]([O:8][CH2:7][C:4]1[CH:3]=[CH:2][CH:1]=[CH:6][CH:5]=1)=[O:10])[CH3:36]

Participants

4

Reactant 2

HCID 6994031(4S)-5-(Benzyloxy)-4-(((benzyloxy)carbonyl)amino)-5-oxopentanoic acidHCID 178525631HCID 178525631, compound

Product 1

HCID 11339684(2S)-2 Benzyloxycarbonylamino-5-oxo-heptanedioic acid 1-benzyl ester 7-ethyl esterYield 40%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Z-Glu-Obzl (a N-α-Cbz-L-glutamic acid α-benzyl ester) (5 g, 13.46 mmol) was dissolved in 50 ml of dry THF at room temperature. N,N′-carbonyl diimidazole (1.1 eq) was added slowly and the mixture was then stirred for 2 hrs at room temperature. Ethyl magnesium malonate (0.55 eq) was added, and the mixture was stirred at room temperature overnight. The product was extracted with ether, and washed with 10% NaHCO3, water, and brine. The residue containing 3 was purified by flash chromatography on silica gel (ethyl acetate:hexanes 50:50) and concentrated on a rotary evaporator to afford a white solid in 40% yield. 1H-NMR (400 MHz, CDCl3): δ 1.26 (t, J=7.2, 3H), 1.9-2.01 (m, 1H), 2.1-2.28 (m, 1H), 2.5-2.7 (m, 2H), 3.37 (s, 2H), 4.18 (q, J=7.2, 2H), 4.41 (s, 1H), 5.11 (s, 2H), 5.18 (s, 2H), 5.44 (d, J=8, 1H), 7.25-7.41 (m, 10H). LC-MS (ESI) calcd for C24H2NO7 (M+H+) 442.18, obsd. 442.0.

Workup

  1. stirringthe mixture was stirred at room temperature overnight
  2. extractionThe product was extracted with ether
  3. washwashed with 10% NaHCO3, water, and brine
  4. additionThe residue containing 3
  5. customwas purified by flash chromatography on silica gel (ethyl acetate:hexanes 50:50)
  6. concentrationconcentrated on a rotary evaporator
  7. customto afford a white solid in 40% yield

Sources & evidence

ORD record
ord-6e2cc3e75fd24d20898ad120176642fa
Source dataset
uspto-grants-2012_06
Patent number
US08192952B2

Reaction notes

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