Hydrochloric Acid → HCID 51034785, compound

HRID 2068236Notes

Reaction equation

HRID 2068236 reaction equation
CS(Cl)(=O)=O.[CH3:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([CH3:13])[C:8]=1[N:14]1[C:18](=[O:19])[CH2:17][C@:16]([CH:23]([CH3:25])[CH3:24])([C:20]([OH:22])=O)[CH2:15]1.C(N(CC)C(C)C)(C)C.[F:35][C:36]([F:49])([F:48])[C:37]1[CH:38]=[C:39]([CH:41]=[C:42]([C:44]([F:47])([F:46])[F:45])[CH:43]=1)[NH2:40].Cl>C1COCC1.C(Cl)Cl>[F:35][C:36]([F:48])([F:49])[C:37]1[CH:38]=[C:39]([NH:40][C:20]([C@@:16]2([CH:23]([CH3:24])[CH3:25])[CH2:17][C:18](=[O:19])[N:14]([C:8]3[C:7]([CH3:6])=[CH:12][CH:11]=[CH:10][C:9]=3[CH3:13])[CH2:15]2)=[O:22])[CH:41]=[C:42]([C:44]([F:45])([F:47])[F:46])[CH:43]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 9480Benzenamine, 3,5-bis(trifluoromethyl)-HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 58218830HCID 58218830, compound

Product 1

HCID 51034785HCID 51034785, compoundYield 63%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Methanesulfonyl chloride (167 mg, 1.45 mmol) was added dropwise to a solution of enantiopure (3R)-1-(2,6-dimethylphenyl)-3-isopropyl-5-oxo-pyrrolidine-3-carboxylic acid (182 mg, 0.661 mmol, prepared in step a above), N,N-diisopropylethylamine (374 mg, 2.90 mmol) and 3,5-bis(trifluoromethyl)aniline (331 mg, 1.45 mmol) in THF (4 mL). Stirring at room temperature for 1 h allowed the reaction to reach completion, whereupon 5 mL of 0.3 M aqueous hydrochloric acid and 10 mL of DCM were added and the mixture was stirred vigorously for 5 min. The separated organic phase was concentrated in vacuo on silica gel and purified by flash chromatography (SiO2, 25-60% EtOAc/hexanes) to give an off-white residue, which was recrystallized from a mixture of hot ethyl acetate (2 mL) and hexanes (7 mL) to give 203 mg of the desired compound (63% yield) as colorless crystals. 1H NMR (400 MHz, CDCl3) 1.09 (d, J=7.4, 3H), 1.11 (d, J=7.4, 3H), 2.13 (s, 3H), 2.23 (s, 3H), 2.26 (qq, J=7.4, 7.4, 1H), 2.81 (d, J=17.2, 1H), 3.09 (d, J=17.2, 1H), 3.61 (d, J=10.4, 1H), 4.17 (d, J=10.4, 1H), 7.02-7.18 (m, 3H), 7.64 (s, 1H), 7.86 (s, 1H), 8.05 (s, 2H). LC-MS: Rt (retention time)=3.10 min, MS: (ES) m/z 487 (M+H+).

Workup

  1. customthe reaction
  2. stirringthe mixture was stirred vigorously for 5 min
  3. concentrationThe separated organic phase was concentrated in vacuo on silica gel
  4. custompurified by flash chromatography (SiO2, 25-60% EtOAc/hexanes)
  5. customto give an off-white residue, which
  6. customwas recrystallized from a mixture of hot ethyl acetate (2 mL) and hexanes (7 mL)

Sources & evidence

ORD record
ord-6b46bf03a64b4b9cb1b13622c716ea53
Source dataset
uspto-grants-2012_10
Patent number
US08293925B2

Reaction notes

Loading…