Dichloromethane → HCID 58641265, compound

HRID 1394956Notes

Reaction equation

HRID 1394956 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[CH2:13][N:12]([C:14](OC(C)(C)C)=O)[C@H:11]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:10]=1.ClCCl.FC(F)(F)C(O)=O.[CH:37]([S:39]([CH3:42])(=[O:41])=[O:40])=C>C(O)C.O1CCOCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[CH2:13][N:12]([CH2:14][CH2:37][S:39]([CH3:42])(=[O:41])=[O:40])[C@H:11]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:10]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 19354Methyl vinyl sulfone2×HCID 58641236HCID 58641236, compound

Product 1

HCID 58641265HCID 58641265, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of tert-butyl (2S)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrole-1-carboxylate (5-5, 100 mg, 0.280 mmol, 1 equiv) in a 4:1 mixture of dichloromethane and trifluoroacetic acid (20 mL) was stirred for 30 min, then concentrated. The residue was partitioned between saturated aqueous sodium bicarbonate solution and ethyl acetate (2×50 mL). The combined organic layers were dried over sodium sulfate and were concentrated. A solution of the residue and methyl vinyl sulfone (0.025 mL, 0.28 mmol, 1.0 equiv) in a 1:1 mixture of dioxane and ethanol (5 mL) was stirred at 23° C. for 16 h. Additional methyl vinyl sulfone (0.025 mL, 0.28 mmol, 1.0 equiv) was added and stirring was continued for 4 h. The reaction mixture was concentrated and the residue was purified by flash column chromatography (hexanes initially, grading to 50% EtOAc in hexanes) to give (2S)-4-(2,5-difluorophenyl)-1-[2-(methylsulfonyl)ethyl]-2-phenyl-2,5-dihydro-1H-pyrrole (37-1) as a white solid. 1H NMR (300 MHz, CDCl3) δ 7.38-7.28 (m, 5H), 7.09-6.89 (m, 3H), 6.28 (br s, 1H), 4.69 (td, 1H, J=4.9, 1.8 Hz), 4.34 (dd, 1H, J=12.5, 4.9 Hz), 3.84 (ddd, 1H, J=13.0, 4.8, 1.7 Hz), 3.36-3.02 (m, 4H), 2.79 (s, 3H). LRMS m/z (M+H) 364.3 found, 364.1 required.

Workup

  1. concentrationconcentrated
  2. customThe residue was partitioned between saturated aqueous sodium bicarbonate solution and ethyl acetate (2×50 mL)
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. concentrationwere concentrated
  5. stirringwas stirred at 23° C. for 16 h
  6. stirringstirring
  7. waitwas continued for 4 h
  8. concentrationThe reaction mixture was concentrated
  9. customthe residue was purified by flash column chromatography (hexanes initially

Sources & evidence

ORD record
ord-b9e847ddf16e45adbf1c2f97388bdc64
Source dataset
uspto-grants-2008_03
Patent number
US07348440B2

Reaction notes

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