tert-Butyl bromoacetate → 3-(Benzyloxycarbonyl)amino-6-isopropyl-1-(tert-butoxycarbonylmethyl)-2-pyridinone
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]=1Participants
Conditions
- Temperature
- 0 °C
Procedure
3-(Benzyloxycarbonyl)amino-6-isopropyl-2 (1H)-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) δ 8.00 (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 C22N28N2O5: 423.2 (M+Na). Found: 423.6.
Workup
- stirringadded-via syringe and the 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-145139b95183407ca1eb20da2c2cdf37
- Source dataset
- uspto-grants-2008_07
- Patent number
- US07402586B2
Reaction notes
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