4-Methylmorpholine → HCID 59708628, compound

HRID 1809148Notes

Reaction equation

HRID 1809148 reaction equation
[CH3:1][Si:2]([CH3:20])([CH3:19])[C:3]1[N:4]=[N:5][N:6]([C:8]2[CH:9]=[C:10]([CH:16]=[CH:17][CH:18]=2)[O:11][CH2:12][C:13]([OH:15])=O)[CH:7]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.CN1CCOCC1.[NH2:52][C:53]1[CH:54]=[CH:55][C:56]([Cl:63])=[C:57]([C:59]([F:62])([F:61])[F:60])[CH:58]=1>C(OCC)(=O)C.CN(C=O)C>[Cl:63][C:56]1[CH:55]=[CH:54][C:53]([NH:52][C:13](=[O:15])[CH2:12][O:11][C:10]2[CH:16]=[CH:17][CH:18]=[C:8]([N:6]3[CH:7]=[C:3]([Si:2]([CH3:1])([CH3:20])[CH3:19])[N:4]=[N:5]3)[CH:9]=2)=[CH:58][C:57]=1[C:59]([F:60])([F:61])[F:62]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 675744-Chloro-3-(trifluoromethyl)anilineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59708590HCID 59708590, compound

Product 1

HCID 59708628HCID 59708628, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a 25 mL recovery flask was added [3-(4-Trimethylsilanyl-[1,2,3]triazol-1-yl)-phenoxy]-acetic acid 6 (483 mg, 1.66 mmol, 1.0 eq.) and a stirbar. O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (1.26 g, 3.3 mmol, 2.0 eq.), DMF (8 mL), and N-methylmorpholine (503 μL, 4.98 mmol, 3.0 eq.) were added. The mixture was stirred at room temperature for 30 min. 5-amino-2-chlorobenzotrifluoride (649 mg, 3.3 mmol, 2.0 eq.) was added and the reaction mixture was stirred overnight at room temperature. The reaction mixture was diluted with ethyl acetate (100 mL) and washed with a succession of 10% aq. LiCl (3×50 mL), H2O (50 mL), and sat'd aq. NaCl (50 mL). The organic phase was dried over anhydrous Na2SO4, filtered, and concentrated to give a grayish solid. The solid was recrystallized in hot MeOH to give a light gray solid, which by LC/MS was a mixture of product and the corresponding de-silylated material (200 mg). The mixture was taken on to the next step without further purification. LC/MSD (HP Series 1100 MSD) MS (ES+) m/z 469.1 (M+H)+1

Workup

  1. stirringthe reaction mixture was stirred overnight at room temperature
  2. washwashed with a succession of 10% aq. LiCl (3×50 mL), H2O (50 mL)
  3. dry with materialThe organic phase was dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a grayish solid
  7. customThe solid was recrystallized in hot MeOH
  8. customto give a light gray solid, which by LC/MS
  9. additiona mixture of product
  10. customThe mixture was taken on to the next step without further purification

Sources & evidence

ORD record
ord-39b439dbd88d4a749920b1886a8df160
Source dataset
uspto-grants-2013_01
Patent number
US08362017B2

Reaction notes

Loading…