2,2,2-Trifluoroethanol → Tert-butyl 4-((4-((4-hydroxybenzyl)amino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-yl)amino)benzoate

HRID 1485649Notes

Reaction equation

HRID 1485649 reaction equation
Cl[C:2]1[N:7]=[C:6](Cl)[N:5]=[C:4](Cl)[N:3]=1.[F:10][C:11]([F:15])([F:14])[CH2:12][OH:13].N1C(C)=CC(C)=CC=1C.[NH2:25][C:26]1[CH:38]=[CH:37][C:29]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[CH:28][CH:27]=1.CCN(C(C)C)C(C)C.[NH2:48][CH2:49][C:50]1[CH:55]=[CH:54][C:53]([OH:56])=[CH:52][CH:51]=1>CC(C)=O.CN1C(=O)CCC1.O>[OH:56][C:53]1[CH:54]=[CH:55][C:50]([CH2:49][NH:48][C:2]2[N:7]=[C:6]([O:13][CH2:12][C:11]([F:15])([F:14])[F:10])[N:5]=[C:4]([NH:25][C:26]3[CH:38]=[CH:37][C:29]([C:30]([O:32][C:33]([CH3:34])([CH3:35])[CH3:36])=[O:31])=[CH:28][CH:27]=3)[N:3]=2)=[CH:51][CH:52]=1

Participants

10

Reactant 6

HCID 64092,2,2-TrifluoroethanolHCID 79532,4,6-TrimethylpyridineHCID 7954Cyanuric chlorideHCID 81531DiisopropylethylamineHCID 974724-HydroxybenzylamineHCID 233272Benzoic acid, 4-amino-, 1,1-dimethylethyl ester

Product 1

HCID 58223050Tert-butyl 4-((4-((4-hydroxybenzyl)amino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-yl)amino)benzoateYield 56.3%

Reagents, catalysts & solvents 3

HCID 180AcetoneSolvent2×HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a solution of 2,4,6-trichloro-1,3,5-triazine (8 g) in acetone (250 mL) was added a solution of 2,2,2-trifluoroethanol (4.77 g) and 2,4,6-Collidine (6.31 mL) in acetone (100 mL) dropwise over 20 minutes. The resulting mixture was stirred at room temperature for 16 hours. All the solvents were removed under vacuum to give a residue which was diluted with NMP (100 mL), followed by addition of tert-butyl 4-aminobenzoate (9.22 g) and DIPEA (22.73 mL). After stirring at room temperature for 16 hours, 4-(aminomethyl)phenol (5.88 g) was added. The resulting mixture was stirred for 2 days at room temperature. Then, the mixture was diluted with 300 mL of water and extracted with EtOAc (2×300 mL). The organic layers were combined, washed with brine (2×150 mL), dried over MgSO4 and concentrated. The residue was purified by silica gel column (hexane:EtOAc=3:2) to give tert-butyl 4-(4-(4-hydroxybenzylamino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-ylamino)benzoate (12 g).

Workup

  1. customAll the solvents were removed under vacuum
  2. customto give a residue which
  3. stirringAfter stirring at room temperature for 16 hours
  4. stirringThe resulting mixture was stirred for 2 days at room temperature
  5. extractionextracted with EtOAc (2×300 mL)
  6. washwashed with brine (2×150 mL)
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel column (hexane:EtOAc=3:2)

Sources & evidence

ORD record
ord-80c694af89974e7c908117b626cfc4a7
Source dataset
uspto-grants-2016_08
Patent number
US09422311B2

Reaction notes

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