Water → HCID 11351702, compound

HRID 563842Notes

Reaction equation

HRID 563842 reaction equation
[O:1]=[S:2]1(=[O:27])[C:8]2[CH:9]=[CH:10][C:11](F)=[CH:12][C:7]=2[CH:6]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:5]([OH:20])[C:4]([CH2:23][CH2:24][CH2:25][CH3:26])([CH2:21][CH3:22])[CH2:3]1.C(=O)([O-])[O-].[Cs+].[Cs+].[C:34]([O:38]CC)(=[O:37])[CH2:35][SH:36].O>CN(C=O)C>[O:1]=[S:2]1(=[O:27])[C:8]2[CH:9]=[CH:10][C:11]([S:36][CH2:35][C:34]([OH:38])=[O:37])=[CH:12][C:7]=2[CH:6]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:5]([OH:20])[C:4]([CH2:23][CH2:24][CH2:25][CH3:26])([CH2:21][CH3:22])[CH2:3]1

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 12185Ethyl ThioglycolateHCID 11153524HCID 11153524, compound

Product 1

HCID 11351702HCID 11351702, compoundYield 48.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1,1-Dioxo-3-butyl-3-ethyl-4-hydroxy-5-phenyl-7-fluoro-2,3,4,5-tetrahydrobenzothiepine (prepared according to WO 98/40375; 300 mg, 0.77 mmol) was dissolved in DMF (3 ml) and caesium carbonate (540 mg, 1.66 mmol) was added followed by ethyl thioglycolate (0.17 ml, 1.54 mmol) and the reaction mixture was subjected to microwave irradiation in a Smith Synthesiser at 100° C. for 5 min. The reaction mixture was added to water (25 ml), extracted with DCM (5×5 ml) and concentrated. The crude ethyl ester was dissolved in THF (4 ml) and water (2 ml) and NaOH (1 M, 4 ml) was added. The reaction mixture was stirred at ambient temperature for 6 hours, quenched with HCl (1 M), diluted with water (25 ml) and extracted with DCM (4×5 ml). The combined organic layers were purified with preparative HPLC using MeCN/ammonium acetate buffer as the eluent (50:50) to give the title compound (172 mg, 48%). NMR (400 MHz, DMSO-d6): 0.74 (t, 3H), 0.84 (t, 3H), 1.01 (m, 1), 1.18-1.46 (m, 5H), 1.60 (m, 1H), 2.02 (m, 1H), 3.07/3.12 (ABq, 2H), 3.33/3.39 (ABq, 2H), 3.95 (s, 1H), 5.23 (s, 1H), 6.38 (d, 1H), 7.19 (dd, 1H), 7.34 (m, 1H), 7.42 (m, 4H), 7.73 (d, 1H).

Workup

  1. customirradiation in a Smith Synthesiser at 100° C. for 5 min
  2. extractionextracted with DCM (5×5 ml)
  3. concentrationconcentrated
  4. dissolutionThe crude ethyl ester was dissolved in THF (4 ml)
  5. additionwater (2 ml) and NaOH (1 M, 4 ml) was added
  6. customquenched with HCl (1 M)
  7. additiondiluted with water (25 ml)
  8. extractionextracted with DCM (4×5 ml)
  9. customThe combined organic layers were purified with preparative HPLC

Sources & evidence

ORD record
ord-16ef2da473234e609a56bff6894019e5
Source dataset
uspto-grants-2011_11
Patent number
US08067584B2

Reaction notes

Loading…