Hydrochloric Acid → HCID 59353101, compound

HRID 1914685Notes

Reaction equation

HRID 1914685 reaction equation
[O:1]=[S:2]1(=[O:24])[CH2:7][CH2:6][CH:5]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][C:10]=2[NH:17]C(=O)C(F)(F)F)[CH2:4][CH2:3]1.C(=O)([O-])[O-].[K+].[K+].O.[OH-].[Li+].Cl>CO.O>[O:1]=[S:2]1(=[O:24])[CH2:7][CH2:6][CH:5]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][C:10]=2[NH2:17])[CH2:4][CH2:3]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 168937Lithium hydroxide, monohydrate2×HCID 59353097HCID 59353097, compound

Product 1

HCID 59353101HCID 59353101, compoundYield 88.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Procedure

N-{2-[(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)methyl]-5-methoxyphenyl}-2,2,2-trifluoroacetamide (890 mg; 2.44 mmol; 1 eq) is suspended in MeOH (15 mL). To the yellow-brown suspension is added dropwise a solution of potassium carbonate (403.98 mg; 2.92 mmol; 1.2 eq) in water (4 mL). Immediately, the suspension lighted up. Stirring is continued at room temperature for 1 h. No conversion is observed. Lithium hydroxide monohydrate (112.44 mg; 2.68 mmol; 1.1 eq) is added leading to a turbid solution. Stirring is allowed to continue at room temperature overnight. No conversion is observed. Additional lithium hydroxide monohydrate (511.08 mg; 12.18 mmol; 5 eq) is added as a solution in water (5 mL). Stirring is continued at room temperature for 4 days. The suspension is cooled with an ice-bath and 5 N HCl is added until pH=1. The resulting solution is concentrated under reduced pressure until precipitation started (approx. 5 mL of solution left). n-Heptane is added as anti-solvent and the biphasic system is cooled with an ice-bath. The beige solid obtained is filtered off, rinsed twice with diethyl ether and dried under high vacuo to afford 580 mg (78%) of the title compound as an off-white solid. 1H NMR (DMSO-d6) δ 9.80 (br s, 2H), 7.17 (d, J=8.7 Hz, 1H), 6.94 (d, J=2.6 Hz, 1H), 6.83 (dd, J=8.7 Hz, 2.6 Hz, 1H), 3.73 (s, 3H), 3.03-2.99 (m, 4H), 2.61-2.58 (m, 2H), 2.10-1.98 (m, 1H), 1.91-1.86 (m, 2H), 1.72-1.61 (m, 2H). HPLC (max plot) 95.5%; Rt 1.55 min. LC/MS: (ES+): 270.1.

Workup

  1. stirringStirring
  2. waitto continue at room temperature overnight
  3. stirringStirring
  4. waitis continued at room temperature for 4 days
  5. temperatureThe suspension is cooled with an ice-bath
  6. concentrationThe resulting solution is concentrated under reduced pressure until precipitation
  7. wait(approx. 5 mL of solution left)
  8. additionn-Heptane is added as anti-solvent and the biphasic system
  9. temperatureis cooled with an ice-bath
  10. customThe beige solid obtained
  11. filtrationis filtered off
  12. washrinsed twice with diethyl ether
  13. customdried under high vacuo

Sources & evidence

ORD record
ord-9fcfb01f3d6342eabcfd521143e0ce33
Source dataset
uspto-grants-2013_12
Patent number
US08614215B2

Reaction notes

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