Triethylamine → HCID 44595824, compound

HRID 467980Notes

Reaction equation

HRID 467980 reaction equation
[Cl:1][C:2]1[N:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4](Cl)=[O:5].[Cl:11][C:12]1[CH:24]=[C:23]([Cl:25])[CH:22]=[C:21]([Cl:26])[C:13]=1[O:14][CH2:15][C@@H:16]1[CH2:20][CH2:19][CH2:18][NH:17]1.C(N(CC)CC)C>ClCCl>[Cl:1][C:2]1[C:3]([C:4]([N:17]2[CH2:18][CH2:19][CH2:20][C@H:16]2[CH2:15][O:14][C:13]2[C:21]([Cl:26])=[CH:22][C:23]([Cl:25])=[CH:24][C:12]=2[Cl:11])=[O:5])=[CH:7][CH:8]=[CH:9][N:10]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 27745412-Chloronicotinoyl chlorideHCID 28750082HCID 28750082, compound

Product 1

HCID 44595824HCID 44595824, compoundYield 17.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

At a temperature of 0° C., a solution of 2-chloro-nicotinoyl chloride (0.313 g; 1.78 mmol) in dichloromethane (5 ml) was added dropwise to a stirred solution of (S)-2-(2,4,6-trichloro-phenoxymethyl)-pyrrolidine (0.30 g; 1.78 mmol), which was prepared as described in example P13, and triethylamine (0.50 ml; 3.56 mmol) in dichloromethane (10 ml). The ice bath was removed and reaction mixture was allowed stirring for 16 hours at ambient temperature. Dichloromethane (40 ml) was added to the mixture. The reaction mixture was washed with 2M HCl (40 ml), 1M NaOH (50 ml) and saturated NaCl (50 ml) and then dried over Na2SO4. After removal of the solvent, the residue (0.21 g in the form of an oil) was purified by flash chromatography over silica gel (eluent:cyclohexane/ethyl acetate 1:1). 0.134 g (17.9% of theory) of (2-chloro-pyridin-3-yl)-[(S)-2-(2,4,6-trichloro-phenoxymethyl)-pyrrolidin-1-yl]-methanone was obtained in form of an oil. 1H NMR (400 MHz, CDCl3): δ 1.88-1.97 (m, 1H), 2.10-2.28 (m, 2H), 2.47-2.54 (m, 1H), 3.30-3.41 (m, 2H), 4.21-4.24 (m, 1H), 4.44 (m, 1H), 4.60-4.65 (m, 1H), 7.26 (s, 2H, Ar—H), 7.30-7.34 (m, 1H, Py-H), 7.68-7.72 (m, 1H, Py-H), 8.42-8.44 (m, 1H, Py-H). MS [M+H]+ 419/421/423/425.

Workup

  1. customwas prepared
  2. customThe ice bath was removed
  3. customreaction mixture
  4. washThe reaction mixture was washed with 2M HCl (40 ml), 1M NaOH (50 ml) and saturated NaCl (50 ml)
  5. dry with materialdried over Na2SO4
  6. customAfter removal of the solvent
  7. customthe residue (0.21 g in the form of an oil) was purified by flash chromatography over silica gel (eluent:cyclohexane/ethyl acetate 1:1)

Sources & evidence

ORD record
ord-ec91d1b4da5c4f29860880cc3163fb11
Source dataset
uspto-grants-2014_01
Patent number
US08623902B2

Reaction notes

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