tert-Butyl bromoacetate → 3-(Benzyloxycarbonyl)amino-6-isopropyl-1-(tert-butoxycarbonylmethyl)-2-pyridinone

HRID 48891Notes

Reaction equation

[CH2:1]([O:8][C:9]([NH:11][C:12]1[C:13](=[O:21])[NH:14][C:15]([CH:18]([CH3:20])[CH3:19])=[CH:16][CH:17]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[C:32]([O:36][C:37](=[O:40])[CH2:38]Br)([CH3:35])([CH3:34])[CH3:33]>O1CCCC1>[CH2:1]([O:8][C:9]([NH:11][C:12]1[C:13](=[O:21])[N:14]([CH2:38][C:37]([O:36][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:40])[C:15]([CH:18]([CH3:19])[CH3:20])=[CH:16][CH:17]=1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 0 °C

Procedure

3-(Benzyloxycarbonyl)amino-6-isopropyl-2(1 H)-pyridinone (1.10 g, 3.84 mmol), as prepared in the preceding step, was dissolved in anhydrous tetrahydrofuran (30 mL) and cooled to 0° C. under nitrogen. A 1.0 M solution of lithium bis(trimethylsilyl)amide in hexanes (4.2 mL, 4.2 mmol) was added via syringe and the reaction stirred for one hour. tert-Butylbromoacetate (0.70 mL, 4.3 mmol) was then added via syringe and the reaction stirred at ambient temperature for 16 hours. After concentration in vacuo, the crude product was purified by flash column chromatography (1:1 hexane:ethyl acetate) giving the title compound as a pale yellow oil (1.38 g, 90%). 1H NMR (300 MHz, CDCl3) δ8.00 (br d, 1H, J=7.8 Hz), 7.78 (s, 1H), 7.36 (m, 5H), 6.15 (d, 1H, J=7.9 Hz), 5.19 (s, 2H), 4.79 (s, 2H), 2.72 (m, 1H), 1.46 (s, 9H), 1.26 (s, 3H), 1.23 (s, 3H). Mass spectrum (MALDI-TOF, gentisic acid matrix) calcd. for C22H28N2O5: 423.2 (M+Na). Found: 423.6.

Workup

stirringthe reaction stirred at ambient temperature for 16 hours
concentrationAfter concentration in vacuo
customthe crude product was purified by flash column chromatography (1:1 hexane:ethyl acetate)

Sources & evidence

ORD record: ord-2f1659100c97478bb1b90cea58c45df9
Source dataset: uspto-grants-2004_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06706021B2

Reaction notes

Loading…