Hydrochloric Acid → HCID 11857669, compound

HRID 1710739Notes

Reaction equation

HRID 1710739 reaction equation
Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[O:13][C:14]([CH2:18]O)=[C:15]([CH3:17])[N:16]=2)=[CH:8][CH:7]=1.C([N:22]([CH2:25][CH3:26])[CH2:23][CH3:24])C.[CH3:27]S(Cl)(=O)=O.[Cl-].[NH4+].[I-].[Na+].[NH:36]1[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1.Cl>ClCCl>[CH3:17][C:15]1[N:16]=[C:12]([C:9]2[CH:8]=[CH:7][C:6]([O:5][CH2:4][CH2:3][CH2:2][N:22]3[CH2:23][CH2:24][CH2:27][CH2:26][CH2:25]3)=[CH:11][CH:10]=2)[O:13][C:14]=1[CH2:18][N:36]1[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1

Participants

9

Reactant 7

HCID 313Hydrochloric AcidHCID 5238Sodium IodideHCID 8082PiperidineHCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 31297Methanesulfonyl chlorideHCID 59457470HCID 59457470, compound

Product 1

HCID 11857669HCID 11857669, compoundYield 12%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of {2-[4-(3-chloropropoxy)phenyl]-4-methyl-1,3-oxazol-5-yl}methanol ax61 (330 mg, 1.21 mmol, 1 eq) and triethylamine (187 μl, 1.33 mmol, 1.1 eq) in dichloromethane (25 ml) is cooled to 0° C. (ice bath) and treated dropwise with methanesulfonyl chloride (103 μl, 1.33 mmol, 1.1 eq). The mixture is stirred 1 h at 0° C. and poured into 20 ml of a saturated aqueous solution of ammonium chloride and extracted with dichloromethane. The organic phases are dried over magnesium sulfate and concentrated. The oily residue is taken up in acetonitrile (25 ml) and treated with sodium iodide (18 mg, 0.12 mmol, 0.1 eq) and piperidine (360 μl, 3.64 mmol, 3 eq). The mixture is stirred at 22° C. for 1 h and then heated at 90° C. (oil bath) overnight. After cooling, the mixture is poured into 10 ml of 1 N aqueous hydrogen chloride and extracted with ether. The aqueous phase is then made basic (pH 10) by addition of 3 N aqueous sodium hydroxide, and extracted with ethyl acetate. The ethyl acetate solution is dried over magnesium sulfate and concentrated to yield 310 mg of an orange oil. This oil is purified by chromatography over silicagel (eluent: dichloromethane/methanol/ammonia 98:1.8:0.2) to afford 60 mg of 1-(3-{4-[4-methyl-5-(piperidin-1-ylmethyl)-1,3-oxazol-2-yl]phenoxy}propyl)piperidine 61 as a pale yellow oil.

Workup

  1. extractionextracted with dichloromethane
  2. dry with materialThe organic phases are dried over magnesium sulfate
  3. concentrationconcentrated
  4. stirringThe mixture is stirred at 22° C. for 1 h
  5. temperatureheated at 90° C. (oil bath) overnight
  6. temperatureAfter cooling
  7. extractionextracted with ether
  8. additionby addition of 3 N aqueous sodium hydroxide
  9. extractionextracted with ethyl acetate
  10. dry with materialThe ethyl acetate solution is dried over magnesium sulfate
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-1cc9bbfe97a440108faa1acc52b480ef
Source dataset
uspto-grants-2010_09
Patent number
US07790720B2

Reaction notes

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