Phenol → HCID 56941485, compound

HRID 1529577Notes

Reaction equation

HRID 1529577 reaction equation
[C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[CH2:9][C:10]1[S:11][C:12]2[CH2:13][N:14]([C:19](=[O:27])[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[F:26])[CH2:15][CH2:16][C:17]=2[N:18]=1.C([O-])([O-])=O.[K+].[K+]>C(#N)C>[F:26][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=1[C:19]([N:14]1[CH2:15][CH2:16][C:17]2[N:18]=[C:10]([CH2:9][O:7][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[S:11][C:12]=2[CH2:13]1)=[O:27]

Participants

5

Reactant 3

HCID 996PhenolHCID 11430Potassium CarbonateHCID 66609500HCID 66609500, compound

Product 1

HCID 56941485HCID 56941485, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

Phenol (0.12 g, 1.24 mmol) was added to a stirred solution of 2-(chloromethyl)-5-(2-fluorobenzoyl)-4,5,6,7-tetrahydro-thiazolo[5,4-c]pyridine (0.19 g, 0.62 mmol) and K2CO3 (0.25 g, 1.86 mmol) in ACN (5 mL). The reaction mixture was stirred at 80° C. for 16 hours, filtered and the solvent evaporated in vacuo. The crude product was purified by HPLC on a C18 XBridge 30×100 mm, 5 μm column (gradient elution: 0.1% TFA in ACN/0.1% TFA in H2O). The desired fractions were collected and extracted with a saturated solution of NaHCO3 and the aqueous layer extracted with AcOEt. The combined organic layers were dried (Na2SO4), filtered and the solvent evaporated in vacuo to yield 5-(2-fluorobenzoyl)-4,5,6,7-tetrahydro-2-(phenoxymethyl)-thiazolo[5,4-c]pyridine (95 mg, 42% yield) as a solid. C20H17FN2O2S. 1H NMR (DMSO-d6, T=80° C.) δ ppm 2.81 (br. s., 2 H), 3.79 (br. s., 2 H), 4.76 (br. s., 2 H), 5.32 (s, 2 H), 6.85-7.09 (m, 3 H), 7.10-7.28 (m, 4 H), 7.30-7.39 (m, 1 H), 7.40-7.55 (m, 1 H).

Workup

  1. filtrationfiltered
  2. customthe solvent evaporated in vacuo
  3. customThe crude product was purified by HPLC on a C18 XBridge 30×100 mm, 5 μm column (gradient elution: 0.1% TFA in ACN/0.1% TFA in H2O)
  4. customThe desired fractions were collected
  5. extractionextracted with a saturated solution of NaHCO3
  6. extractionthe aqueous layer extracted with AcOEt
  7. dry with materialThe combined organic layers were dried (Na2SO4)
  8. filtrationfiltered
  9. customthe solvent evaporated in vacuo

Sources & evidence

ORD record
ord-6aaf446dddda4ae6aac477ddb358a5aa
Source dataset
uspto-grants-2015_07
Patent number
US09090632B2

Reaction notes

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