1,2-Dichlorobenzene → 3-Cyclopentyl-2-(3-fluoro-4-methanesulfonyl-phenyl)-propionic acid methyl ester

HRID 398674Notes

Reaction equation

HRID 398674 reaction equation
[F:1][B-](F)(F)F.N#[O+].[CH3:8][O:9][C:10](=[O:29])[CH:11]([C:18]1[CH:23]=[CH:22][C:21]([S:24]([CH3:27])(=[O:26])=[O:25])=[C:20](N)[CH:19]=1)[CH2:12][CH:13]1[CH2:17][CH2:16][CH2:15][CH2:14]1.ClC1C=CC=CC=1Cl>C(Cl)Cl>[CH3:8][O:9][C:10](=[O:29])[CH:11]([C:18]1[CH:23]=[CH:22][C:21]([S:24]([CH3:27])(=[O:26])=[O:25])=[C:20]([F:1])[CH:19]=1)[CH2:12][CH:13]1[CH2:17][CH2:16][CH2:15][CH2:14]1

Participants

5

Reactant 3

HCID 72391,2-DichlorobenzeneHCID 11137142Nitrilooxonium tetrafluoroborateHCID 544385412-(3-Amino-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid methyl ester

Product 1

HCID 536938863-Cyclopentyl-2-(3-fluoro-4-methanesulfonyl-phenyl)-propionic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A slurry of nitrosonium tetrafluoroborate (215 mg, 1.84 mmol) in methylene chloride (6 mL) was cooled to 0° C. and then treated dropwise with a solution of 2-(3-amino-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid methyl ester (500 mg, 1.54 mmol) in a small amount of methylene chloride. The resulting reaction mixture was stirred at 0° C. for 1 h. The reaction mixture was then allowed to warm to 25° C. and was treated with 1,2-dichlorobenzene (6 mL). The resulting reaction mixture was heated at 100° C. for 1 h, during which time, the methylene chloride was distilled off. After 1 h at 100° C., the reaction mixture was allowed to cool to 25° C. The crude reaction mixture was directly purified by flash chromatography (Merck Silica gel 60, 230-400 mesh, 9/1 hexanes/ethyl acetate to elute 1,2-dichlorobenzene then 2/1 hexanes/ethyl acetate) to afford impure 3-cyclopentyl-2-(3-fluoro-4-methanesulfonyl-phenyl)-propionic acid methyl ester as a yellow oil. Repurification by flash chromatography (Merck Silica gel 60, 230-400 mesh, 3/1 hexanes/ethyl acetate) afforded pure 3-cyclopentyl-2-(3-fluoro-4-methanesulfonyl-phenyl)-propionic acid methyl ester (214 mg, 42%) as a pale yellow oil which solidified upon sitting at 25° C. to a pale yellow solid: mp 66-68° C.; EI-HRMS m/e calcd for C16H21FO4S (M+) 328.1144, found 328.1148.

Workup

  1. customThe resulting reaction mixture
  2. temperatureto warm to 25° C.
  3. customThe resulting reaction mixture
  4. temperaturewas heated at 100° C. for 1 h, during which time
  5. distillationthe methylene chloride was distilled off
  6. waitAfter 1 h at 100° C.
  7. temperatureto cool to 25° C
  8. customThe crude reaction mixture
  9. customwas directly purified by flash chromatography (Merck Silica gel 60, 230-400 mesh, 9/1 hexanes/ethyl acetate
  10. washto elute 1,2-dichlorobenzene

Sources & evidence

ORD record
ord-3b8bd42b3bba41ba9484a2a249f34950
Source dataset
uspto-grants-2003_08
Patent number
US06610846B1

Reaction notes

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