Triethylamine → Methyl 1-[(2E)-3-(2,5-difluorophenyl)prop-2-en-1-yl]-4-[3-(6-cyano-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)propyl]piperidine-3-carboxylate

HRID 1644414Notes

Reaction equation

HRID 1644414 reaction equation
FC(F)(F)C(O)=O.[C:8]([C:10]1[CH:11]=[CH:12][C:13]2[O:18][CH2:17][C:16](=[O:19])[N:15]([CH2:20][CH2:21][CH2:22][CH:23]3[CH2:28][CH2:27][NH:26][CH2:25][CH:24]3[C:29]([O:31][CH3:32])=[O:30])[C:14]=2[CH:33]=1)#[N:9].[F:34][C:35]1[CH:40]=[CH:39][C:38]([F:41])=[CH:37][C:36]=1/[CH:42]=[CH:43]/[CH:44]=O.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)(Cl)Cl.CO.C(OCC)(=O)C.O>[F:34][C:35]1[CH:40]=[CH:39][C:38]([F:41])=[CH:37][C:36]=1/[CH:42]=[CH:43]/[CH2:44][N:26]1[CH2:27][CH2:28][CH:23]([CH2:22][CH2:21][CH2:20][N:15]2[C:14]3[CH:33]=[C:10]([C:8]#[N:9])[CH:11]=[CH:12][C:13]=3[O:18][CH2:17][C:16]2=[O:19])[CH:24]([C:29]([O:31][CH3:32])=[O:30])[CH2:25]1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 66774489methyl 4-[3-(6-cyano-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)propyl]piperidine-3-carboxylate trifluoroacetate2×HCID 86642138(2E)-3-(2,5-difluorophenyl)-2-propenal

Product 1

HCID 15982403Methyl 1-[(2E)-3-(2,5-difluorophenyl)prop-2-en-1-yl]-4-[3-(6-cyano-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)propyl]piperidine-3-carboxylateYield 32.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 21584188Chloroform methanolSolvent

Conditions

Temperature
0 °C

Procedure

A solution of methyl 4-[3-(6-cyano-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)propyl]piperidine-3-carboxylate trifluoroacetate (Intermediate 130, crude, 171, 0.48 mmol), (2E)-3-(2,5-difluorophenyl)acrylaldehyde [FR 2872164] (81 mg, 0.48 mmol), and triethylamine (0.13 mL. 0.96 mmol) in chloroform/methanol (6 mL, 10:1) was heated over 3 Å molecular sieves at 70° C. for 3 hours. The reaction mixture was cooled to 0° C., and sodium triacetoxy borohydride (200 mg, 0.94 mmol) was added. The resulting reaction mixture was allowed to warm to room temperature and stir for 18 hours. The reaction was diluted with ethyl acetate (25 mL) and water (10 mL). The aqueous phase was separated and washed twice with ethyl acetate. The organic layers were combined, dried over magnesium sulfate and evaporated at reduced pressure. Chromatography on silica gel with diethyl ether gave the title compound as a off-white foam, (79 mg, 32%).

Workup

  1. customThe resulting reaction mixture
  2. temperatureto warm to room temperature
  3. customThe aqueous phase was separated
  4. washwashed twice with ethyl acetate
  5. dry with materialdried over magnesium sulfate
  6. customevaporated at reduced pressure

Sources & evidence

ORD record
ord-3e8b1dd32fec4d6eb0a190e79aa99878
Source dataset
uspto-grants-2012_02
Patent number
US08124602B2

Reaction notes

Loading…