Ethyl bromoacetate → Ethyl [7-(4-t-butoxycarbonylpiperazin-1-yl)-3,4-dihydro-1(1H)-isoquinolinone-2-yl]acetate

HRID 862673Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:23]=[C:22]3[C:17]([CH2:18][CH2:19][NH:20][C:21]3=[O:24])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].Br[CH2:36][C:37]([O:39][CH2:40][CH3:41])=[O:38].CCOC(C)=O>C1COCC1.CCCCCC.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][N:11]([C:14]2[CH:23]=[C:22]3[C:17]([CH2:18][CH2:19][N:20]([CH2:36][C:37]([O:39][CH2:40][CH3:41])=[O:38])[C:21]3=[O:24])=[CH:16][CH:15]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: -78 °C

Procedure

A solution of 7-(4-t-butoxycarbonylpiperazin-1-yl)-3,4-dihydro-1(1H)-isoquinolinone (1-3) (2.37 g, 7.16 mmol) in THF (30 mL) at -78° C. under argon was treated with NaHMDS (1M solution in THF; 7.88 mL, 7.88 mmol) and the temperature was allowed to rise to -50° C. over 30 minutes. The solution was cooled back to -78° C. and ethyl bromoacetate (1.19 mL, 10.7 mmol) was added in one lot. After stirring at ambient temperature for 3 hours, the mixture was poured into EtOAc, extracted with 1N HCl, washed with brine (twice), dried (MgSO4) and evaporated to give an oil. Column chromatography (hexane/EtOAc 1:1 then 1:2) gave 1-4 as a solid. Rf (silica; hexane/EtOAc 1:1)=0.38.

Workup

extractionextracted with 1N HCl
washwashed with brine (twice),
dry with materialdried (MgSO4)
customevaporated
customto give an oil

Sources & evidence

ORD record: ord-a46f41fb97b140aaa16c88ec0ad95e9b
Source dataset: uspto-grants-1998_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05719162

Reaction notes

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