Acetonitrile → Methyl (3r,4s)-1-[(z)-1-(methylthio)-2-nitrovinyl]-4-[(3r)-3-phenylpyrrolidin-1-yl]carbonylpiperidine-3-carboxylate

HRID 535089

Reaction equation

HRID 535089 reaction equation
[CH3:1][O:2][C:3]([C@@H:5]1[C@@H:10]([C:11]([N:13]2[CH2:17][CH2:16][C@H:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH2:14]2)=[O:12])[CH2:9][CH2:8][NH:7][CH2:6]1)=[O:4].C(#N)C.C(N(CC)CC)C.[CH3:34][S:35][C:36](SC)=[CH:37][N+:38]([O-:40])=[O:39]>>[CH3:34][S:35]/[C:36](/[N:7]1[CH2:8][CH2:9][C@H:10]([C:11]([N:13]2[CH2:17][CH2:16][C@H:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH2:14]2)=[O:12])[C@@H:5]([C:3]([O:2][CH3:1])=[O:4])[CH2:6]1)=[CH:37]\[N+:38]([O-:40])=[O:39]

Participants

5

Reactant 4

HCID 6342AcetonitrileHCID 8471TriethylamineHCID 836231,1-Bis(methylthio)-2-nitroethyleneHCID 67304902(3r,4s)-4-((r)-3-Phenyl-pyrrolidine-1-carbonyl)-piperidine-3-carboxylic acid methyl ester

Product 1

HCID 67304566Methyl (3r,4s)-1-[(z)-1-(methylthio)-2-nitrovinyl]-4-[(3r)-3-phenylpyrrolidin-1-yl]carbonylpiperidine-3-carboxylateYield 53.4%

Conditions

Temperature
85 °C

Procedure

To a stirred solution of (3R,4S)-4-((R)-3-phenyl-pyrrolidine-1-carbonyl)-piperidine-3-carboxylic acid methyl ester (3.10E2 mg, 0.000980 mol) in anhydrous acetonitrile (9.8 mL, 0.19 mol) at rt was added triethylamine (274 uL, 0.00196 mol) and 1,1-bis(methylthio)-2-nitroethylene (248 mg, 0.00147 mol). The reaction mixture was heated to reflux (oil bath temperature: 85° C.) for 19 h. The reaction mixture was concentrated in vacuo. The residue was purified by Combiflash with 40-95% EtOAc/Hex to give the product as a yellow viscous oil (227 mg, 53% in yield). MS (ESI): (M+H)+=434.1.

Workup

  1. temperatureThe reaction mixture was heated
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customThe residue was purified by Combiflash with 40-95% EtOAc/Hex

Sources & evidence

ORD record
ord-29da9d92aa9f44a8ae644a0d3bb384bc
Source dataset
uspto-grants-2014_10
Patent number
US08853243B2

Linked notes

Loading…