Oxalyl chloride → HCID 20872671, compound

HRID 1828832Notes

Reaction equation

HRID 1828832 reaction equation
[Cl:1][C:2]1[N:10]=[CH:9][C:8]([F:11])=[CH:7][C:3]=1[C:4]([OH:6])=O.C(Cl)(=O)C(Cl)=O.[C:18]([O:22][C:23](=[O:32])[NH:24][CH:25]1[CH2:30][CH2:29][CH:28]([NH2:31])[CH2:27][CH2:26]1)([CH3:21])([CH3:20])[CH3:19]>ClCCl.CN(C)C=O>[C:18]([O:22][C:23](=[O:32])[NH:24][CH:25]1[CH2:26][CH2:27][CH:28]([NH:31][C:4]([C:3]2[C:2]([Cl:1])=[N:10][CH:9]=[C:8]([F:11])[CH:7]=2)=[O:6])[CH2:29][CH2:30]1)([CH3:21])([CH3:19])[CH3:20]

Participants

6

Reactant 3

HCID 65578Oxalyl chlorideHCID 2756050Cis tert-Butyl 4-aminocyclohexylcarbamateHCID 114352432-Chloro-5-fluoronicotinic acid

Product 1

HCID 20872671HCID 20872671, compoundYield 39.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

2-Chloro-5-fluoro nicotinic acid (3.00 g, 0.017 mol) (see Preparation 41), was dissolved in dichloromethane (100 ml) and N,N-dimethylformamide (1 drop) was added, followed by oxalyl chloride (3.0 ml, 0.034 mol). The reaction mixture was held at room temperature for 4 hours, after which time the solvent was removed in vacuo. The residue was suspended in dichloromethane (100 ml) and triethylamine (5 ml) added followed by addition of (4-amino-cyclohexyl)-carbamic acid tert-butyl ester (5.40 g, 0.026 mol) (Preparation 42a). The reaction mixture was then held under an atmosphere of nitrogen at room temperature for a further 18 hours. The reaction mixture was then washed with water (100 ml) and the organic phase dried over anhydrous magnesium sulphate. The solvent was removed in vacuo, and the residue triturated with ethyl acetate/pentane (1:1, by volume, 10 ml) giving {4-[(2-chloro-5-fluoro-pyridine-3-carbonyl)amino]-cyclohexyl}-carbamic acid tert-butyl ester (2.5 g, 80:20 syn:anti) as a white solid.

Workup

  1. customafter which time the solvent was removed in vacuo
  2. additiontriethylamine (5 ml) added
  3. waitThe reaction mixture was then held under an atmosphere of nitrogen at room temperature for a further 18 hours
  4. washThe reaction mixture was then washed with water (100 ml)
  5. dry with materialthe organic phase dried over anhydrous magnesium sulphate
  6. customThe solvent was removed in vacuo
  7. customthe residue triturated with ethyl acetate/pentane (1:1, by volume, 10 ml)

Sources & evidence

ORD record
ord-de9b1adcfd8546709669d23cde96a697
Source dataset
uspto-grants-2006_06
Patent number
US07060717B2

Reaction notes

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