Dimethylamine → HCID 11649761, compound

HRID 1028620Notes

Reaction equation

HRID 1028620 reaction equation
[F:1][C:2]1[C:7]([CH:8]([CH3:10])[CH3:9])=[CH:6][C:5]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][C:12]=2[CH2:21][N:22]2[C@@H:26]([CH3:27])[C@@H:25]([C:28]3[CH:29]=[C:30]([CH:33]=[CH:34][CH:35]=3)[CH:31]=O)[O:24][C:23]2=[O:36])=[C:4]([O:37][CH3:38])[CH:3]=1.[CH3:39][NH:40][CH3:41].[BH4-].[Na+]>CCO.CO.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[CH3:39][N:40]([CH2:31][C:30]1[CH:29]=[C:28]([C@H:25]2[O:24][C:23](=[O:36])[N:22]([CH2:21][C:12]3[CH:13]=[C:14]([C:17]([F:20])([F:19])[F:18])[CH:15]=[CH:16][C:11]=3[C:5]3[CH:6]=[C:7]([CH:8]([CH3:10])[CH3:9])[C:2]([F:1])=[CH:3][C:4]=3[O:37][CH3:38])[C@H:26]2[CH3:27])[CH:35]=[CH:34][CH:33]=1)[CH3:41]

Participants

7

Reactant 3

HCID 674DimethylamineHCID 4311764Sodium borohydrideHCID 11562778HCID 11562778, compound

Product 1

HCID 11649761HCID 11649761, compound

Reagents, catalysts & solvents 3

HCID 11026Titanium isopropoxideCatalystHCID 702EthanolSolventHCID 887MethanolSolvent

Procedure

To a solution of 3-((4S,5R)-3-{[4′-fluoro-5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-methyl-2-oxo-1,3-oxazolidin-5-yl)benzaldehyde (15 mg, 0.028 mmol) in EtOH (1 mL) was added dimethylamine (140 μL of a 2.0 M solution in MeOH) and titanium isopropoxide (79 μL, 0.28 mmol). The resulting white suspension was stirred overnight. Sodium borohydride (7.1 mg, 0.188 mmol) was added and the mixture was stirred overnight. The reaction was quenched by pouring the mixture into 2N aqueous ammonia (2 mL). The resulting inorganic precipitate was filtered and washed with dichloromethane. The combined filtrates were extracted with dichloromethane (2×15 mL). The extracts were dried (Na2SO4) and concentrated in vacuo. The residue was purified by flash chromatography (Si) to give (4S,5R)-5-{3-[(dimethylamino)methyl]phenyl}-3-{[4′-fluoro-5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one. LCMS calc.=559.25; found=559.4 (M+1)+. 1H NMR (500 MHz, CDCl3, 1:1 mixture of atropisomers) δ 7.74 (s, 0.5 H); 7.67 (s, 0.5 H); 7.64 (s, 0.5 H); 7.62 (s, 0.5 H); 7.37-7.29 (m, 3 H); 7.18 (s, 1 H); 7.16 (s, 0.5 H); 7.13 (s, 0.5 H); 7.01 (d, J=8.4 Hz, 0.5 H); 6.99 (d, J=8.5 Hz, 0.5 H); 6.71 (d, J=3.0 Hz, 0.5 H); 6.68 (d, J=2.9 Hz, 0.5 H); 5.52 (d, J=8.1 Hz, 0.5 H); 5.37 (d, J=8.0 Hz, 0.5 H); 4.82 (d, J=15.9 Hz, 0.5 H); 4.77 (d, J=16.0 Hz, 0.5 H); 4.15 (d, J=16.0 Hz, 0.5 H); 3.91 (d, J=15.9 Hz, 0.5 H); 3.76 (s, 3 H); 3.80-3.73 (m, 0.5 H); 3.72-3.68 (m, 0.5H); 3.43 (s, 2H); 3.25-3.18 (m, 1 H); 2.23 (s, 6 H); 1.27 (m, 4.5 H); 1.19 (d, J=6.9 Hz, 1.5 H); 0.53 (d, J=6.5 Hz, 1.5 H); 0.39 (d, J=6.6 Hz, 1.5 H).

Workup

  1. stirringthe mixture was stirred overnight
  2. customThe reaction was quenched
  3. additionby pouring the mixture into 2N aqueous ammonia (2 mL)
  4. filtrationThe resulting inorganic precipitate was filtered
  5. washwashed with dichloromethane
  6. extractionThe combined filtrates were extracted with dichloromethane (2×15 mL)
  7. dry with materialThe extracts were dried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by flash chromatography (Si)

Sources & evidence

ORD record
ord-88d3ffe845984689b69284fd789c099b
Source dataset
uspto-grants-2014_05
Patent number
US08735435B2

Reaction notes

Loading…