Methyl isocyanoacetate → 6-isocyano-6,7-dihydro-5H-[1]pyrindine-6-carboxylic acid methyl ester
Reaction equation
[CH3:1][O:2][C:3](=[O:7])[CH2:4][N+:5]#[C-:6].Cl[CH2:9][C:10]1[C:15]([CH2:16]Cl)=[CH:14][CH:13]=[CH:12][N:11]=1.CC(C)([O-])C.[K+]>CN(C=O)C>[CH3:1][O:2][C:3]([C:4]1([N+:5]#[C-:6])[CH2:9][C:10]2[N:11]=[CH:12][CH:13]=[CH:14][C:15]=2[CH2:16]1)=[O:7]Participants
Procedure
Isocyano-acetic acid methyl ester (112 mg, 1.13 mmol) and 2,3-bis-chloromethyl-pyridine (200 mg, 1.14 mmol) were dissolved in DMF. Potassium tert-butoxide (0.255 g, 2.27 mmol) was added and the reaction mixture was stirred for 1 h at room temperature. The mixture was partitioned between EA and a saturated aqueous sodium hydrogencarbonate solution, the aqueous phase extracted with EA, and the organic extracts were dried over sodium sulfate, filtered and evaporated to dryness. The residue was purified by silica gel chromatography (HEP/EA gradient) to give 6-isocyano-6,7-dihydro-5H-[1]pyrindine-6-carboxylic acid methyl ester. This compound was added to a solution of thionyl chloride (147 mg, 1.23 mmol) in ethanol (1 ml) and refluxed overnight. The mixture was evaporated to dryness, and the residue was stirred with HEP, filtered and dried in vacuo. The obtained product was reacted with 4-methoxy-3-(2-m-tolyl-ethoxy)-benzoic acid in analogy to step 1 of example 15 and the title compound purified by preparative RP HPLC (water/ACN gradient).
Workup
- customThe mixture was partitioned between EA
- extractiona saturated aqueous sodium hydrogencarbonate solution, the aqueous phase extracted with EA
- dry with materialthe organic extracts were dried over sodium sulfate
- filtrationfiltered
- customevaporated to dryness
- customThe residue was purified by silica gel chromatography (HEP/EA gradient)
Sources & evidence
- ORD record
- ord-16c7e03f137f49f8988fec688edd3983
- Source dataset
- uspto-grants-2014_08
- Patent number
- US08802720B2
Reaction notes
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