Diisopropylethylamine → tert-Butyl 8-(2-(trifluoromethyl)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate

HRID 1253706Notes

Reaction equation

HRID 1253706 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]([F:11])([F:10])[F:9])[N:3]=1.[CH2:12]1[C:16]2([CH2:21][CH2:20][NH:19][CH2:18][CH2:17]2)[CH2:15][CH2:14][N:13]1[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23].CCN(C(C)C)C(C)C>C(O)(C)C>[F:9][C:8]([F:11])([F:10])[C:4]1[N:3]=[C:2]([N:19]2[CH2:20][CH2:21][C:16]3([CH2:12][N:13]([C:22]([O:24][C:25]([CH3:26])([CH3:27])[CH3:28])=[O:23])[CH2:14][CH2:15]3)[CH2:17][CH2:18]2)[CH:7]=[CH:6][N:5]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 152943694-Chloro-2-(trifluoromethyl)pyrimidineHCID 34178604tert-Butyl 2,8-diazaspiro[4.5]decane-2-carboxylate

Product 1

HCID 66701106tert-Butyl 8-(2-(trifluoromethyl)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-2-carboxylateYield 47%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

4-Chloro-2-(trifluoromethyl)pyrimidine (2.72 mmol, 1 eq.) and isopropanol (4 ml) were introduced into a microwave vessel. tert-Butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (2.72 mmol, 1 eq.) and DIPEA (0.6 ml, 6.8 mmol), 2.5 eq.) were added in succession and the reaction mixture was introduced into a microwave oven at 75° C. for 45 min. After TLC control, the reaction mixture was concentrated on a rotary evaporator. A reddish liquid remained and was diluted with methylene chloride (200 ml). The organic phase was washed with water (2×100 ml) and sat. NaCl solution (50 ml), dried over sodium sulfate and concentrated. The brown liquid residue was purified by column chromatography (silica gel, ethyl acetate). Yield: 47%

Workup

  1. additionthe reaction mixture was introduced into a microwave oven at 75° C. for 45 min
  2. concentrationAfter TLC control, the reaction mixture was concentrated on a rotary evaporator
  3. additionwas diluted with methylene chloride (200 ml)
  4. washThe organic phase was washed with water (2×100 ml) and sat. NaCl solution (50 ml)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customThe brown liquid residue was purified by column chromatography (silica gel, ethyl acetate)

Sources & evidence

ORD record
ord-f3690e2832664a2c9bc72ab92c5b9028
Source dataset
uspto-grants-2013_06
Patent number
US08455475B2

Reaction notes

Loading…