1,2-Dichloroethane → HCID 24765482, compound

HRID 2383528Notes

Reaction equation

HRID 2383528 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([C@H:8]([CH3:12])[C:9]([OH:11])=O)[CH:5]=[CH:4][C:3]=1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[Cl-].[CH3:20][O:21][C:22]1[CH:23]=[CH:24][C:25]([C@H:28]([NH3+:30])[CH3:29])=[N:26][CH:27]=1.C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C>CN(C=O)C.C(Cl)Cl>[F:1][C:2]1[CH:7]=[C:6]([C@H:8]([CH3:12])[C:9]([NH:30][C@@H:28]([C:25]2[CH:24]=[CH:23][C:22]([O:21][CH3:20])=[CH:27][N:26]=2)[CH3:29])=[O:11])[CH:5]=[CH:4][C:3]=1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 72099(+)-FlurbiprofenHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 178490623HCID 178490623, compound

Product 1

HCID 24765482HCID 24765482, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 0.70 g (2.87 mmol) (S)-(+)-2-fluoro-alpha-methyl-4-biphenylacetic acid in 6.00 ml DMF was added 0.60 g (3.15 mmol) (1R)-1-(5-methoxypyridin-2-yl)ethanaminium chloride, 0.51 g (3.73 mmol) HOAT, 0.71 g (3.73 mmol) EDC, and 1.50 mL (8.60 mmol) DIEA. After 2.00 h at room temperature, the reaction mixture was diluted with CH2Cl2, washed three times with water, and washed with brine. The organic layer was dried over NaSO4, filtered and concentrated in vacuo. Purification by flash chromatography (1×14 cm silica gel, linear gradient 30-65% EtOAc:hexane) afforded (2S)-2-(2-fluoro-1,1′-biphenyl-4-yl)-N-[(1R)-1-(5-methoxypyridin-2-yl)ethyl]propanamide. 1H NMR (CDCl3, 400 MHz) δ 8.19 (m, 1H); 7.56-7.54 (m, 2H); 7.46-7.34 (m, 4H); 7.20-7.14 (m, 4H); 6.78 (br d, 1H, J=7.33 Hz); 5.09 (m, 1H); 3.85 (s, 1H); 3.60 (q, 1H, J=7.15 Hz, 14.29 Hz); 1.53 (d, 3H, J=7.14); 1.37 (d, 3H, J=6.77 Hz). HRMS (ES) exact mass calcd for C23H23FN2O2: 379.1817, Found: 379.1817.

Workup

  1. washwashed three times with water
  2. washwashed with brine
  3. dry with materialThe organic layer was dried over NaSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by flash chromatography (1×14 cm silica gel, linear gradient 30-65% EtOAc:hexane)

Sources & evidence

ORD record
ord-41bc2f7128514101b76514df2a2d325c
Source dataset
uspto-grants-2012_09
Patent number
US08263627B2

Reaction notes

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