Ethanethiol → 1-Isopropyl-3-hydroxy-5-[3-(trifluoromethyl)-4-chlorophenyl]-2(1H)-pyridone

HRID 625936Notes

Reaction equation

HRID 625936 reaction equation
C([O:8][C:9]1[C:10](=[O:29])[N:11]([CH:26]([CH3:28])[CH3:27])[CH:12]=[C:13]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[C:17]([C:22]([F:25])([F:24])[F:23])[CH:16]=2)[CH:14]=1)C1C=CC=CC=1.C(S)C.B(F)(F)F.O(CC)CC>C(Cl)Cl.CO>[Cl:21][C:18]1[CH:19]=[CH:20][C:15]([C:13]2[CH:14]=[C:9]([OH:8])[C:10](=[O:29])[N:11]([CH:26]([CH3:28])[CH3:27])[CH:12]=2)=[CH:16][C:17]=1[C:22]([F:25])([F:23])[F:24]

Participants

6

Reactant 3

HCID 6343EthanethiolHCID 8000Boron trifluoride etherateHCID 674185543-(benzyloxy)-5-[4-chloro-3-(trifluoromethyl)phenyl]-1-(propan-2-yl)pyridin-2(1H)-one

Product 1

HCID 533798091-Isopropyl-3-hydroxy-5-[3-(trifluoromethyl)-4-chlorophenyl]-2(1H)-pyridoneYield 36%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of crude 3-(benzyloxy)-5-[4-chloro-3-(trifluoromethyl)phenyl]-1-(propan-2-yl)pyridin-2(1H)-one (86 mg) in CH2Cl2 (1 mL) was added ethanethiol (0.075 mL, 1.019 mmol) then BF3—OEt2 (0.13 mL, 1.026 mmol) at RT. After 5 h the mixture was diluted with MeOH and concentrated. The residue was taken up in DMSO:H2O and purified by preparative reversed-phase HPLC (20×150 mm Waters Sunfire (0.1% TFA), 5-70% CH3CN/water over 20 min at 20 mL/min) to give the title compound (24 mg, 36%) as a light tan solid. 1H NMR (500 MHz, d6-DMSO): δ 9.28 (s, 1 H); 7.97 (s, 1 H); 7.92 (dd, J=8.4, 2.2 Hz, 1 H); 7.74 (d, J=8.4 Hz, 1 H); 7.68 (d, J=2.4 Hz, 1 H); 7.14 (d, J=2.4 Hz, 1 H); 5.18-5.11 (m, 1 H); 1.39 (d, J=6.8 Hz, 6 H). HRMS (ES) calc (M+H)+=332.0660, found 332.0661.

Workup

  1. customat RT
  2. concentrationconcentrated
  3. customH2O and purified by preparative reversed-phase HPLC (20×150 mm Waters Sunfire (0.1% TFA), 5-70% CH3CN/water over 20 min at 20 mL/min)

Sources & evidence

ORD record
ord-8d4a9e882c0b433d8cb84a8e1c36dee4
Source dataset
uspto-grants-2016_04
Patent number
US09309199B2

Reaction notes

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