1,2-Dichloroethane → 4-Chloro-2-methyl-N-[2-methyl-1-phenyl-2-(1-pyrrolidinyl)propyl]-6-(methylthio)benzamide

HRID 20838Notes

Reaction equation

HRID 20838 reaction equation
[CH3:1][C:2]([N:12]1[CH2:16][CH2:15][CH2:14][CH2:13]1)([CH3:11])[CH:3]([NH2:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[Cl:17][C:18]1[CH:26]=[C:25]([S:27][CH3:28])[C:21]([C:22](O)=[O:23])=[C:20]([CH3:29])[CH:19]=1.O.ON1C2C=CC=CC=2N=N1.C(Cl)CCl>C(Cl)Cl>[Cl:17][C:18]1[CH:26]=[C:25]([S:27][CH3:28])[C:21]([C:22]([NH:10][CH:3]([C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=2)[C:2]([CH3:1])([N:12]2[CH2:13][CH2:14][CH2:15][CH2:16]2)[CH3:11])=[O:23])=[C:20]([CH3:29])[CH:19]=1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 27960291-Hydroxybenzotriazole hydrateHCID 25158607[2-Methyl-1-phenyl-2-(1-pyrrolidinyl)propyl]amineHCID 685404964-Chloro-2-methyl-6-(methylthio)benzoic acid

Product 1

HCID 593478944-Chloro-2-methyl-N-[2-methyl-1-phenyl-2-(1-pyrrolidinyl)propyl]-6-(methylthio)benzamideYield 66.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of (+)-[2-methyl-1-phenyl-2-(1-pyrrolidinyl)propyl]amine D6 (262 mg; 1.2 mmol), 4-chloro-2-methyl-6-(methylthio)benzoic acid (388 mg; 1.8 mmol), 1-hydroxybenzotriazole hydrate (276 mg; 1.8 mmol) and EDC (345 mg; 1.8 mmol) in DCM (16 ml) was stirred for 16 h. The reaction mixture was then partitioned between DCM and saturated aqueous sodium hydrogen carbonate and the organic layer separated, washed with brine, dried and evaporated. The residue was chromatographed on silica gel eluting with an ethyl acetate-hexane 0 to 100% gradient to give the title compound as a colourless oil (332 mg; 66%). 1H NMR (CDCl3) δ: 0.90 (3H, s), 0.98 (3H, s), 1.66-1.75 (4H, m), 2.31 (3H, s), 2.44 (3H, s), 2.60-2.65 (2H, m), 2.69-2.74 (2H, m), 4.82 (1H, d J=3 Hz), 7.00 (1H, m), 7.09 (1H, m), 7.11 (1H, br s), 7.23-7.33 (3H, m), 7.41-7.43 (2H, m). Mass Spectrum (Electrospray LC/MS): Found 417 (MH+). C23H2935ClN2OS requires 416. Ret. time 2.08 min. The product was dissolved in methanol and 1M HCl/diethylether solution was added dropwise to the stirred solution. After stirring at room temperature for 5 minutes, the mixture was evaporated at reduced pressure. It was redissolved in DCM and evaporated again at reduced pressure to yield the hydrochloride salt as a white foam (320 mg).

Workup

  1. customThe reaction mixture was then partitioned between DCM and saturated aqueous sodium hydrogen carbonate
  2. customthe organic layer separated
  3. washwashed with brine
  4. customdried
  5. customevaporated
  6. customThe residue was chromatographed on silica gel eluting with an ethyl acetate-hexane 0 to 100% gradient

Sources & evidence

ORD record
ord-52225a70b5854f56ba6809b95ca1d2de
Source dataset
uspto-grants-2010_06
Patent number
US07745642B2

Reaction notes

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