Sodium hydride → Ethyl 1-[1-(tert-butoxycarbonyl)propyl]-7-oxo-4-azepanecarboxylate

HRID 7401Notes

Reaction equation

[O:1]=[C:2]1[NH:8][CH2:7][CH2:6][CH:5]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:4][CH2:3]1.Br[CH:15]([CH2:23][CH3:24])[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17].[H-].[Na+]>C(#N)C>[C:19]([O:18][C:16]([CH:15]([N:8]1[C:2](=[O:1])[CH2:3][CH2:4][CH:5]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:6][CH2:7]1)[CH2:23][CH3:24])=[O:17])([CH3:22])([CH3:21])[CH3:20]

Participants

Conditions

Temperature: 50 °C

Procedure

In a 150 ml three necked flask fitted with reflux condenser, magnetic stirrer and dropping funnel under inert atmosphere, 5.09 g (27.5 mmoles, 1 eq) of ethyl 7-oxo-4-azepanecarboxylate 28 and 12.27 g (55 mmoles, 2 eq) of tert-butyl 2-bromobutanoate were dissolved in 70 ml of acetonitrile. The temperature was raised to 50° C. and 1.32 g (55 mmoles, 2 eq) of sodium hydride were added portionwise (exothermic). The mixture was stirred one more hour at 50° C. and concentrated to dryness, the residue was poured on ice/water and neutralised with solid ammonium chloride. The mixture was extracted three times with CH2Cl2, the combined organic phases were dried over magnesium sulfate, filtered and concentrated to dryness. The residue was purified by PrepLC (1 kg SiO2, CH2Cl2/MTBE, 85/15) to give 8.5 g of pure diester 29, 69% yield.

Workup

temperaturewith reflux condenser, magnetic stirrer
concentrationconcentrated to dryness
additionthe residue was poured on ice/water and neutralised with solid ammonium chloride
extractionThe mixture was extracted three times with CH2Cl2
dry with materialthe combined organic phases were dried over magnesium sulfate
filtrationfiltered
concentrationconcentrated to dryness
customThe residue was purified by PrepLC (1 kg SiO2, CH2Cl2/MTBE, 85/15)

Sources & evidence

ORD record: ord-82f8dd09f130443ab0aefbeeb0485fd7
Source dataset: uspto-grants-2006_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07087596B2

Reaction notes

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