4-(4-Bromophenyl)-1,3-thiazol-2-amine → Methyl N-[4-(4-bromophenyl)-1,3-thiazol-2-yl]-3,3,3-trifluoroalaninate

HRID 1436392Notes

Reaction equation

HRID 1436392 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]([NH2:13])[S:11][CH:12]=2)=[CH:4][CH:3]=1.[CH3:14][O:15][C:16](=[O:23])[C:17]([C:19]([F:22])([F:21])[F:20])=O.C([BH3-])#N.[Na+]>C(Cl)Cl.CO.[Ti](Cl)(Cl)(Cl)Cl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:9]=[C:10]([NH:13][C@H:17]([C:16]([O:15][CH3:14])=[O:23])[C:19]([F:22])([F:21])[F:20])[S:11][CH:12]=2)=[CH:6][CH:7]=1

Participants

7

Reactant 3

HCID 6206834-(4-Bromophenyl)-1,3-thiazol-2-amineHCID 2734931Methyl 3,3,3-trifluoro-2-oxopropanoateHCID 5003444Sodium cyanoborohydride

Product 1

HCID 86618600Methyl N-[4-(4-bromophenyl)-1,3-thiazol-2-yl]-3,3,3-trifluoroalaninateYield 44%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

4-(4-Bromophenyl)-1,3-thiazol-2-ylamine (510 mg, 2.0 mmol) and methyl-3,3,3-trifluoropyruvate (0.10 mL, 1.0 mmol) were dissolved in 50 mL methylene chloride. Titanium (IV) chloride (1M in toluene, 1.6 mL, 1.6 mmol) was added dropwise to give an orange-brown suspension. The mixture was stirred for 15 min and then added by cannula to a solution of sodium cyanoborohydride (0.26 g, 3.0 mmol) in 50 mL of methanol. The mixture was stirred for 15 min and then quenched by the addition of H2O and saturated aqueous sodium bicarbonate. The mixture was extracted three times with methylene chloride. The organics were combined, washed with water, brine, dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. Flash chromatography (100% methylene chloride) afforded methyl N-[4-(4-bromophenyl)-1,3-thiazol-2-yl]-3,3,3-trifluoroalaninate (0.17 g, 44%) as a white solid. MS (ES) m/z 392.8.

Workup

  1. customto give an orange-brown suspension
  2. stirringThe mixture was stirred for 15 min
  3. customquenched by the addition of H2O and saturated aqueous sodium bicarbonate
  4. extractionThe mixture was extracted three times with methylene chloride
  5. washwashed with water, brine
  6. dry with materialdried over anhydrous MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-fb8315d3e04f4b7ca6e7ccf310ca097c
Source dataset
uspto-grants-2009_11
Patent number
US07618990B2

Reaction notes

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