4-Methylmorpholine → 4-{3-Chloro-4-[2-(2-chloro-pyridin-4-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-benzoylamino}-benzoic acid methyl ester

HRID 1095882Notes

Reaction equation

HRID 1095882 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[CH:11]([CH3:25])[C:12]([C:18]1[CH:23]=[CH:22][N:21]=[C:20]([Cl:24])[CH:19]=1)([OH:17])[C:13]([F:16])([F:15])[F:14])[C:5](O)=[O:6].[CH3:26][O:27][C:28](=[O:36])[C:29]1[CH:34]=[CH:33][C:32]([NH2:35])=[CH:31][CH:30]=1.CN1CCOCC1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C)C=O.O>[CH3:26][O:27][C:28](=[O:36])[C:29]1[CH:34]=[CH:33][C:32]([NH:35][C:5](=[O:6])[C:4]2[CH:8]=[CH:9][C:10]([CH:11]([CH3:25])[C:12]([C:18]3[CH:23]=[CH:22][N:21]=[C:20]([Cl:24])[CH:19]=3)([OH:17])[C:13]([F:16])([F:14])[F:15])=[C:2]([Cl:1])[CH:3]=2)=[CH:31][CH:30]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 12082Methyl 4-aminobenzoateHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 574212683-Chloro-4-[2-(2-chloro-pyridin-4-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-benzoic acid

Product 1

HCID 866459444-{3-Chloro-4-[2-(2-chloro-pyridin-4-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-benzoylamino}-benzoic acid methyl esterYield 42.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-chloro-4-[2-(2-chloro-pyridin-4-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-benzoic acid (80 mg, 0.2 mmol) and 4-amino-benzoic acid methylester (34 mg, 0.22 mmol) in N,N-dimethylformamide (4 ml) were added 4-methylmorpholine (62 mg, 0.61 mmol) and HBTU (115 mg, 0.3 mmol). The mixture was stirred for 17 h at room temperature. The reaction solution was poured in water, extracted twice with AcOEt, washed with brine, dried over MgSO4, filtered and concentrated. The residue was purified by flash chromatography (5 g silica gel, heptane/AcOEt 4:1) to give the title compound (45 mg) as a white solid. MS (m/e)=527.1 [M+H+].

Workup

  1. extractionextracted twice with AcOEt
  2. washwashed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography (5 g silica gel, heptane/AcOEt 4:1)

Sources & evidence

ORD record
ord-35d40321156645dc8436b51879380e59
Source dataset
uspto-grants-2012_03
Patent number
US08138189B2

Reaction notes

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