Diethyl Pyrocarbonate → 2-[ethyl-(4-fluorophenyl)sulfonyl-amino]-N-[[3-[4-(trifluoromethoxy)phenyl]phenyl]methyl]prop-2-enamide

HRID 1479822Notes

Reaction equation

HRID 1479822 reaction equation
[CH2:1]([N:3]([S:9]([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=1)(=[O:11])=[O:10])[C:4](=[CH2:8])[C:5]([OH:7])=O)[CH3:2].CCOC(OC(OCC)=O)=O.[F:30][C:31]([F:48])([F:47])[O:32][C:33]1[CH:38]=[CH:37][C:36]([C:39]2[CH:40]=[C:41]([CH2:45][NH2:46])[CH:42]=[CH:43][CH:44]=2)=[CH:35][CH:34]=1>C1COCC1>[CH2:1]([N:3]([S:9]([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=1)(=[O:11])=[O:10])[C:4](=[CH2:8])[C:5]([NH:46][CH2:45][C:41]1[CH:42]=[CH:43][CH:44]=[C:39]([C:36]2[CH:37]=[CH:38][C:33]([O:32][C:31]([F:30])([F:47])[F:48])=[CH:34][CH:35]=2)[CH:40]=1)=[O:7])[CH3:2]

Participants

5

Reactant 3

HCID 3051Diethyl PyrocarbonateHCID 61032752(4'-(Trifluoromethoxy)-[1,1'-biphenyl]-3-yl)methanamineHCID 903842012-[Ethyl-(4-fluorophenyl)sulfonyl-amino]prop-2-enoic acid

Product 1

HCID 783202182-[ethyl-(4-fluorophenyl)sulfonyl-amino]-N-[[3-[4-(trifluoromethoxy)phenyl]phenyl]methyl]prop-2-enamideYield 24%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of acid 4B (0.35 g, 1.28 mmol) in THF (25 mL) was added with DEPC (0.25 mL, 1.3 mol eq) and the mixture was stirred at room temperature for 10′. Then [3-[4-(trifluoromethoxy)phenyl]phenyl]methanamine 23B (0.376 g, 1.1 mol eq) and a catalytic amount of TEA were added, then the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, water (40 mL) was added to the residue that is extracted with EtOAc (3×25 mL) and washed with brine (1×40 mL). The separated organic phase was anydrified over Na2SO4, evaporated to dryness and the residue was purified by flash chromatography (1:1 EtOAc:Petroleum ether) to afford a white solid (0.15 g) after recrystallization from ethyl ether. Yield=24%, 1HNMR (DMSO, 200 MHz) δ 1.08 (t, 3H, J=8), 3.37 (q, 2H, J=7.5), 4.44 (d, 2H, J06.1), 5.16 (s, 1H), 6.09 (s, 1H), 7.32 (d, 1H), 7.46 (m, 5H), 7.53 (d, 1H), 7.62 (s, 1H), 7.76 (dd, 2H), 7.86 (m, 2H), 8.78 (t, 1H); [M+1] 522.51 (C25H22F4N2O4S requires 522.12).

Workup

  1. stirringthe reaction mixture was stirred at room temperature overnight
  2. customThe solvent was removed under reduced pressure, water (40 mL)
  3. additionwas added to the residue that
  4. extractionis extracted with EtOAc (3×25 mL)
  5. washwashed with brine (1×40 mL)
  6. customevaporated to dryness
  7. customthe residue was purified by flash chromatography (1:1 EtOAc:Petroleum ether)

Sources & evidence

ORD record
ord-71898a139293460d905e0d816cdbf629
Source dataset
uspto-grants-2016_08
Patent number
US09409864B2

Reaction notes

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