Triethylamine → 4-(2-Azetidin-1-yl-ethyl)-2-(4-bromo-phenyl)-5-methyl-oxazole

HRID 1445826Notes

Reaction equation

HRID 1445826 reaction equation
CS(Cl)(=O)=O.[Br:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[O:14][C:15]([CH3:21])=[C:16]([CH2:18][CH2:19]O)[N:17]=2)=[CH:9][CH:8]=1.C([N:24]([CH2:27][CH3:28])[CH2:25]C)C.BrC1C=CC(C2OC(C)=C(CCOS(C)(=O)=O)N=2)=CC=1.N1CCC1>ClCCl.O1CCCC1>[N:24]1([CH2:19][CH2:18][C:16]2[N:17]=[C:13]([C:10]3[CH:11]=[CH:12][C:7]([Br:6])=[CH:8][CH:9]=3)[O:14][C:15]=2[CH3:21])[CH2:25][CH2:28][CH2:27]1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 10422AzetidineHCID 31297Methanesulfonyl chlorideHCID 108805302-(2-(4-Bromophenyl)-5-methyloxazol-4-YL)ethanolHCID 11451238Methanesulfonic acid 2-[2-(4-bromo-phenyl)-5-methyl-oxazol-4-yl]-ethyl ester

Product 1

HCID 115007244-(2-Azetidin-1-yl-ethyl)-2-(4-bromo-phenyl)-5-methyl-oxazoleYield 76%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Add methanesulfonyl chloride (0.745 g, 6.50 mmol) to a cool (0° C.) solution of 2-[2-(4-bromo-phenyl)-5-methyl-oxazol-4-yl]-ethanol (1.4 g, 5.0 mmol) and triethylamine (1.26 g, 12.5 mmol) in dichloromethane (20 mL). Warm to room temperature and stir for 1 hour. Remove solvents, transfer crude of methanesulfonic acid 2-[2-(4-bromo-phenyl)-5-methyl-oxazol-4-yl]-ethyl ester residue to a sealed tube, add tetrahydrofuran (30 mL), azetidine (2.0 g, 35.5 mmol), and heat at 60° C. overnight. Wash the crude organic material with 1N HCl. Separate layers and add 5N NaOH to the aqueous layer until it is basic. Extract the aqueous layer with diethyl ether (2×50 mL), dry the organic extracts over Na2SO4, filter, and concentrate. Purify on silica gel eluting with 10% ammoniated methanol in dichloromethane to give 4-(2-azetidin-1-yl-ethyl)-2-(4-bromo-phenyl)-5-methyl-oxazole (1.22 g, 72%): mass spectrum (m/e): 323 (M+1).

Workup

  1. temperatureheat at 60° C. overnight
  2. washWash the crude organic material with 1N HCl
  3. additionSeparate layers and add 5N NaOH to the aqueous layer until it
  4. extractionExtract the aqueous layer with diethyl ether (2×50 mL)
  5. dry with materialdry the organic extracts over Na2SO4
  6. filtrationfilter
  7. concentrationconcentrate
  8. customPurify on silica gel eluting with 10% ammoniated methanol in dichloromethane

Sources & evidence

ORD record
ord-2a4f467e0c2f48649be280e6854f237e
Source dataset
uspto-grants-2010_02
Patent number
US07666871B2

Reaction notes

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