Acetaldehyde → rac-[(3R,4S)-3-(3,4-Dichloro-phenyl)-4-ethylamino-pyrrolidin-1-yl]-[1-(1-methyl-cyclopropanecarbonyl)-piperidin-4-yl]-methanone

HRID 527473Notes

Reaction equation

HRID 527473 reaction equation
[NH2:1][CH:2]1[CH:6]([C:7]2[CH:12]=[CH:11][C:10]([Cl:13])=[C:9]([Cl:14])[CH:8]=2)[CH2:5][N:4]([C:15]([CH:17]2[CH2:22][CH2:21][N:20]([C:23]([C:25]3([CH3:28])[CH2:27][CH2:26]3)=[O:24])[CH2:19][CH2:18]2)=[O:16])[CH2:3]1.[CH:29](=O)[CH3:30].C([BH3-])#N.[Na+]>C(O)C>[Cl:14][C:9]1[CH:8]=[C:7]([C@H:6]2[C@H:2]([NH:1][CH2:29][CH3:30])[CH2:3][N:4]([C:15]([CH:17]3[CH2:22][CH2:21][N:20]([C:23]([C:25]4([CH3:28])[CH2:27][CH2:26]4)=[O:24])[CH2:19][CH2:18]3)=[O:16])[CH2:5]2)[CH:12]=[CH:11][C:10]=1[Cl:13]

Participants

5

Reactant 3

HCID 177AcetaldehydeHCID 5003444Sodium cyanoborohydrideHCID 67238593rac-(3S,4R)-[3-Amino-4-(3,4-dichloro-phenyl)-pyrrolidin-1-yl]-[1-(1-methyl-cyclopropanecarbonyl)-piperidin-4-yl]-methanone

Product 1

HCID 67237915rac-[(3R,4S)-3-(3,4-Dichloro-phenyl)-4-ethylamino-pyrrolidin-1-yl]-[1-(1-methyl-cyclopropanecarbonyl)-piperidin-4-yl]-methanoneYield 56%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of rac-(3S,4R)-[3-Amino-4-(3,4-dichloro-phenyl)-pyrrolidin-1-yl]-[1-(1-methyl-cyclopropanecarbonyl)-piperidin-4-yl]-methanone (50 mg, 0.12 mmol) in ethanol (0.3 mL) were added acetaldehyde (10 uL, 0.18 mmol) and sodiumcyanoborohydride (15 mg, 0.24 mmol) and the reaction mixture was stirred at ambient temperature for 3 h. It was concentrated and the residue separated between water and ethylacetate. The organic layer was dried over sodium sulfate and concentrated. Purification by chromatography (SiO2, dichloromethane:methanol=100:0 to 95:5) afforded the title compound (30 mg, 56%) as a light yellow oil. MS m/e: 452.3 [M]+.

Workup

  1. concentrationIt was concentrated
  2. customthe residue separated between water and ethylacetate
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. concentrationconcentrated
  5. customPurification by chromatography (SiO2, dichloromethane:methanol=100:0 to 95:5)

Sources & evidence

ORD record
ord-b726b62f1cf84a4090fb11197ce01823
Source dataset
uspto-grants-2016_05
Patent number
US09346786B2

Reaction notes

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