3-(Trifluoromethoxy)benzaldehyde → [1-(3-Trifluoromethoxy-benzyl)-piperidin-4-yl]-(5-trifluoromethyl-[1,3,4]thiadiazol-2-yl)-amine

HRID 1426385Notes

Reaction equation

HRID 1426385 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([NH:7][C:8]2[S:9][C:10]([C:13]([F:16])([F:15])[F:14])=[N:11][N:12]=2)[CH2:3][CH2:2]1.[F:17][C:18]([F:29])([F:28])[O:19][C:20]1[CH:21]=[C:22]([CH:25]=[CH:26][CH:27]=1)[CH:23]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C>ClCCCl>[F:17][C:18]([F:28])([F:29])[O:19][C:20]1[CH:21]=[C:22]([CH:25]=[CH:26][CH:27]=1)[CH2:23][N:1]1[CH2:6][CH2:5][CH:4]([NH:7][C:8]2[S:9][C:10]([C:13]([F:16])([F:14])[F:15])=[N:11][N:12]=2)[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 6051393-(Trifluoromethoxy)benzaldehydeHCID 2724942TriacetoxyborohydrideHCID 59323569Piperidin-4-yl-(5-trifluoromethyl-[1,3,4]thiadiazol-2-yl)-amine

Product 1

HCID 25054944[1-(3-Trifluoromethoxy-benzyl)-piperidin-4-yl]-(5-trifluoromethyl-[1,3,4]thiadiazol-2-yl)-amineYield 68%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A mixture of piperidin-4-yl-(5-trifluoromethyl-[1,3,4]thiadiazol-2-yl)-amine (D4) (0.025 g, 0.10 mmol), 3-trifluoromethoxy-benzaldehyde (0.034 ml, 0.29 mmol) and polymer supported triacetoxyborohydride (2.07 mmol/g) (0.165 g, 0.29 mmol) in 1,2-dichloroethane (2 ml) was shaken at room temperature for 16 h. After this period, the reaction mixture was filtered through an Isolute SCX-2 cartridge. The cartridge was washed with methanol. The crude product was eluted with a 7M solution of ammonia in methanol. The solvent was evaporated in vacuo. The crude product was purified by flash column chromatography (silica gel; 5% ammonia in methanol (7M)/dichloromethane) to yield E13 (0.029 g, 68%) as a white solid. C16H16F6N4OS requires 426. Found 427 (MH+).

Workup

  1. waitAfter this period
  2. filtrationthe reaction mixture was filtered through an Isolute SCX-2 cartridge
  3. washThe cartridge was washed with methanol
  4. washThe crude product was eluted with a 7M solution of ammonia in methanol
  5. customThe solvent was evaporated in vacuo
  6. customThe crude product was purified by flash column chromatography (silica gel; 5% ammonia in methanol (7M)/dichloromethane)

Sources & evidence

ORD record
ord-7a505adf3f0743f39b80047728359553
Source dataset
uspto-grants-2015_01
Patent number
US08933101B2

Reaction notes

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