Water → Ethyl 4-(3-cyano-2,3,4,5-tetrahydrooxepin-3-yl)piperazine-1-carboxylate

HRID 1943012Notes

Reaction equation

HRID 1943012 reaction equation
[O:1]1[CH:7]=[CH:6][CH2:5][CH2:4][C:3](=O)[CH2:2]1.[Si]([C:13]#[N:14])(C)(C)C.O.[CH2:16]([O:18][C:19]([N:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1)=[O:20])[CH3:17]>CO.[I-].[Zn+2].[I-]>[C:13]([C:3]1([N:24]2[CH2:23][CH2:22][N:21]([C:19]([O:18][CH2:16][CH3:17])=[O:20])[CH2:26][CH2:25]2)[CH2:4][CH2:5][CH:6]=[CH:7][O:1][CH2:2]1)#[N:14]

Participants

7

Reactant 4

HCID 962WaterHCID 84311-Piperazinecarboxylic acid, ethyl esterHCID 82115Trimethylsilyl cyanideHCID 584159144,5-Dihydrooxepin-3(2h)-one

Product 1

HCID 58415949Ethyl 4-(3-cyano-2,3,4,5-tetrahydrooxepin-3-yl)piperazine-1-carboxylateYield 58.4%

Reagents, catalysts & solvents 2

HCID 9883512zinc(II)iodideCatalystHCID 887MethanolSolvent

Procedure

4,5-Dihydrooxepin-3(2H)-one (220 mg, 1.962 mmole) and zinc iodide (31 mg, 0.097 mmole) were combined neat. To this was added TMSCN (0.28 ml, 2.089 mmole) slowly (cooling with cold water bath). After 1 hr a solution of 1-ethoxycarbonylpiperazine (0.32 ml, 2.195 mmole) in MeOH (10 ml) was added then the mixture was heated to reflux. After 16 hr the mixture was cooled to RT and concentrated. Flash column chromatography (25% EtOAc/hexanes) gave the title compound as a clear oil (320 mg, 58%). 1H-NMR (CDCl3, 500 MHz) 6.32 (d, J=6.34 Hz, 1 H), 4.80 (m, 1 H), 4.31 (d, J=12.94 Hz, 1 H), 4.15 (m, 3 H), 3.55 (bs, 4 H), 2.64 (bs, 4 H), 2.30 (bs, 3 H), 2.16 (m, 1 H), 1.27 (t, J=7.08 Hz, 3 H).

Workup

  1. additionTo this was added
  2. temperaturethe mixture was heated to reflux
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-c4ae80b09fe9495e92c6c4ac174409d5
Source dataset
uspto-grants-2013_03
Patent number
US08389720B2

Reaction notes

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