Bis-(1H-imidazol-2-YL)-methanone → (2S)-2 Benzyloxycarbonylamino-5-oxo-heptanedioic acid 1-benzyl ester 7-ethyl ester

HRID 1429309Notes

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:28]([C:35]1NC=CN=1)(C1NC=CN=1)=[O:29].C([O-])(=O)[CH2:41][C:42]([O-])=[O:43].C([Mg+2])C>C1COCC1>[CH2:42]([O:43][C:28](=[O:29])[CH2:35][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])[CH3:41]

Participants

Conditions

Temperature: 0 °C

Procedure

Z-Glu-Obzl 3 (1.0 g, 2.7 mmol) was dissolved in dry THF (10 mL) at rt. Carbonyl diimidazole (0.48 g, 2.96 mmol) was added slowly and the mixture was then stirred for another 2 h. After the solution was cooled to 0° C., ethyl magnesium malonate solution 2 (4.7 mL, 1.2 mmol) was added, and the mixture was then stirred at rt overnight. The product was extracted with ester, and washed with 10% NaHCO3, water, and brine. After the solvent was evaporated, the residue was purified by flash chromatography on silica gel (Hexanes:EtOAc=1:1) and afford a white solid (0.9 g, 2.03 mmol, 75.2%). 1H NMR (400 MHz, CDCl3, 25° C.) δ 1.23 (t, 3H), 1.90-2.00 (m, 1H), 2.10-2.30 (m, 1H), 2.50-2.70 (m, 2H), 3.36 (s, 2H), 4.16 (q, 2H), 4.30-4.50 (m, 1H), 5.10 (s, 2H), 5.12 (s, 2H) 5.36 (m, 1H), 7.25-7.40 (m, 10H).

Workup

stirringthe mixture was then stirred at rt overnight
extractionThe product was extracted with ester
washwashed with 10% NaHCO3, water, and brine
customAfter the solvent was evaporated
customthe residue was purified by flash chromatography on silica gel (Hexanes:EtOAc=1:1)

Sources & evidence

ORD record: ord-5923b3e5a22f454190d86180b1a0601b
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08940506B2

Reaction notes

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