Oxalyl chloride → HCID 178451075, compound

HRID 1035731Notes

Reaction equation

HRID 1035731 reaction equation
[C:1]([O:5][C:6]([CH2:8][C@H:9]1[CH2:14][CH2:13][C@H:12]([C:15]2[CH:23]=[CH:22][C:18]([C:19](O)=[O:20])=[CH:17][CH:16]=2)[CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)(=O)C([Cl:27])=O>ClCCl.CN(C)C=O>[Cl:27][C:19]([C:18]1[CH:22]=[CH:23][C:15]([C@H:12]2[CH2:13][CH2:14][C@H:9]([CH2:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:10][CH2:11]2)=[CH:16][CH:17]=1)=[O:20]

Participants

5

Reactant 2

HCID 65578Oxalyl chlorideHCID 178451081HCID 178451081, compound

Product 1

HCID 178451075HCID 178451075, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

0.400 g of trans-4-(4-tert-butoxycarbonylmethylcyclohexyl)benzoic acid (1.26 mmol, 1 eq.) is placed in 8 mL of dichloromethane with stirring, at room temperature, under a nitrogen atmosphere. 0.21 mL of oxalyl chloride (2.51 mmol, 2 eq.) and 2 drops of dimethylformamide are successively added. The reaction medium is stirred for 2 hours and concentrated under vacuum. The tert-butyl trans-4-(4-chlorocarbonylphenyl)cyclohexaneacetate formed is dissolved in 15 mL of acetone and placed under nitrogen. The mixture is cooled in an ice bath and 0.147 g of potassium thiocyanate (1.51 mmol, 1.2 eq.) is added. The reaction mixture is stirred at room temperature for 2 hours. 0.669 g of 2-[(3R,6S/3S,6R)-5,5-dimethylhexahydro-1′H-spiro[1,3-dioxane-2,2′-pentalen]-5′-yl]acetohydrazide (2.37 mmol, 1.89 eq.) dissolved in 10 mL of acetone is then added and the mixture is refluxed for 16 hours. The reaction medium is diluted with dichloromethane and washed three times with water. The organic phase is dried over sodium sulfate and concentrated under vacuum. The residue is chromatographed on silica gel, eluting with a mixture of ethyl acetate and heptane in a 1/2 ratio. After triturating in ethanol, 0.286 g of tert-butyl (trans-4-{4-[(5-{[(3R,6S/3S,6R)-5-ethoxyoctahydropentalen-2-yl]methyl}-1,3,4-thiadiazol-2-yl)carbamoyl]phenyl}cyclohexyl)acetate is obtained.

Workup

  1. stirringThe reaction medium is stirred for 2 hours
  2. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-5f505693ed94450583dd107f47845f39
Source dataset
uspto-grants-2013_10
Patent number
US08546391B2

Reaction notes

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