Ethyl chloroformate → HCID 53952976, compound

HRID 1584888Notes

Reaction equation

HRID 1584888 reaction equation
[CH3:1][C:2]1[C:7]([C:8]([OH:10])=O)=[CH:6][CH:5]=[CH:4][N:3]=1.ClC(OCC)=O.[NH2:17][CH2:18][CH:19]1[CH2:24][CH2:23][N:22]([CH2:25][C@@H:26]2[O:31][C:30]3[CH:32]=[C:33]([Cl:36])[CH:34]=[CH:35][C:29]=3[O:28][CH2:27]2)[CH2:21][CH2:20]1>ClCCl.C(N(CC)CC)C.CO>[Cl:36][C:33]1[CH:34]=[CH:35][C:29]2[O:28][CH2:27][C@H:26]([CH2:25][N:22]3[CH2:21][CH2:20][CH:19]([CH2:18][NH:17][C:8]([C:7]4[C:2]([CH3:1])=[N:3][CH:4]=[CH:5][CH:6]=4)=[O:10])[CH2:24][CH2:23]3)[O:31][C:30]=2[CH:32]=1

Participants

7

Reactant 3

HCID 10928Ethyl chloroformateHCID 6433732-Methylnicotinic acidHCID 11000970HCID 11000970, compound

Product 1

HCID 53952976HCID 53952976, compoundYield 23.7%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent3×HCID 8471TriethylamineSolvent2×

Procedure

Triethylamine (0.47 ml) was added to a suspension of 2-methylpyridine-3-carboxylic acid (0.46 g) in dichloromethane and the mixture cooled in ice water. Ethyl chloroformate (0.33 ml) was added with stirring and the mixture allowed to warm to ambient temperature during 18 hours. (S)-4-(Aminomethyl)-1-(7-chloro-1,4-benzodioxan-2-ylmethyl)piperidine (1.0 g) was added and stirring continued for 24 hours. The solvent was evaporated and the residue triturated with water, collected by filtration, and purified by flash chromatography over silica eluting with a 3:1, then a 2:1, then a 1:1 mixture of ethyl acetate and methanol. Appropriate fractions were combined and the solvent removed in vacuo to give still impure product. Repeat flash chromatography over silica eluting with a 10:1 mixture of dichloromethane and methanol, then an 18:1:1 mixture of dichloromethane, methanol and triethylamine, followed by removal of solvent in vacuo from the appropriate fractions, gave (S)-N-{[1-(7-chloro-1,4-benzodioxan-2-ylmethyl)-4-piperidyl]methyl}-2-methylpyridine-3-carboxamide (330 mg) as a colourless solid m.p. 133-136° C. [α]D -46.6° (c=0.837, methanol).

Workup

  1. stirringstirring
  2. customThe solvent was evaporated
  3. customthe residue triturated with water
  4. filtrationcollected by filtration
  5. custompurified by flash chromatography over silica eluting with a 3:1
  6. additiona 2:1, then a 1:1 mixture of ethyl acetate and methanol
  7. customthe solvent removed in vacuo
  8. customto give still impure product
  9. customfollowed by removal of solvent in vacuo from the appropriate fractions

Sources & evidence

ORD record
ord-ff05718b573d489ea2d70cc152c1d6fc
Source dataset
uspto-grants-1999_08
Patent number
US05935973

Reaction notes

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