Water → 2-Chloro-4-[[(1S,2R)-2-hydroxycyclohexyl]amino]-3-methyl-benzonitrile

HRID 245076

Reaction equation

HRID 245076 reaction equation
[Cl:1][C:2]1[C:9]([CH3:10])=[C:8](F)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].Cl.[NH2:13][C@H:14]1[CH2:19][CH2:18][CH2:17][CH2:16][C@H:15]1[OH:20].C(=O)(O)[O-].[Na+].O>CS(C)=O.Cl>[Cl:1][C:2]1[C:9]([CH3:10])=[C:8]([NH:13][C@H:14]2[CH2:19][CH2:18][CH2:17][CH2:16][C@H:15]2[OH:20])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5]

Participants

7

Reactant 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 12228413(1R,2S)-2-aminocyclohexan-1-ol hydrochlorideHCID 445509712-Chloro-4-fluoro-3-methylbenzonitrile

Product 1

HCID 866937852-Chloro-4-[[(1S,2R)-2-hydroxycyclohexyl]amino]-3-methyl-benzonitrileYield 68%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 679Dimethyl SulfoxideSolvent

Procedure

A solution of 2-chloro-4-fluoro-3-methyl-benzonitrile (500 mg, 2.95 mmol), (1R,2S)-2-aminocyclohexanol hydrochloride (671 mg, 4.42 mmol, Small Molecules, Inc.) and sodium bicarbonate (991 mg, 11.8 mmol) in DMSO (14.7 mL), and water (2.1 mL) is heated at 130° C. for 48 h. After cooling to room temperature, the mixture is diluted with 1 N HCl and extracted twice with EtOAc. The organic layers are combined, dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting residue is purified using radial chromatography, eluting with 2% methanol/dichloromethane to furnish the title compound as an off-white solid (527 mg, 68%). LC-ES/MS m/z 265.2 (M+1).

Workup

  1. extractionextracted twice with EtOAc
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe resulting residue is purified
  6. washeluting with 2% methanol/dichloromethane

Sources & evidence

ORD record
ord-ec65236738ad4f70a18c4c5f6f6088e9
Source dataset
uspto-grants-2014_02
Patent number
US08658693B2

Linked notes

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