HCID 23458310, compound → HCID 3029408, compound

HRID 1679994Notes

Reaction equation

HRID 1679994 reaction equation
[Cl:1][CH2:2][CH2:3][NH:4][CH2:5][CH:6]([OH:23])[CH:7]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[O:15][CH3:16].C([Li])CCC>C1COCC1.CCCCCC>[ClH:1].[CH3:16][O:15][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=1[O:8][CH:7]([CH:6]1[O:23][CH2:2][CH2:3][NH:4][CH2:5]1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

5

Reactant 2

HCID 23458310HCID 23458310, compoundHCID 178418339Butyllithium

Product 1

HCID 3029408HCID 3029408, compoundYield 35.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Procedure

3.35 g of N-(2-chloro-ethyl)-2-hydroxy-3-phenyl-3-(2-methoxy-phenoxy)-propylamine was dissolved in 40 ml of anhydrous THF at -10° C. At this temperature, slow dropwise addition was made to the mixture of 6.07 ml of 15% butyl lithium in hexane. After approximately 2 hours at -10° C. the temperature was slowly allowed to return to room temperature and the whole was stirred for another 20 hours in these conditions, and then concentrated to dryness. The residue was dissolved in ethyl ether, filtered and the filtrate again concentrated to dryness. The residue was converted to the hydrochloride by treatment with gaseous HCl in ethyl ether. After three crystallizations from a mixture of isopropanol and a very small quantity of ethyl ether, there was obtained 1.2 g of 2-[α-(2-methoxy-phenoxy)-benzyl]-morpholine hydrochloride, melting point 112°-170° C. (Yield 35.7%) as a mixture of diastereoisomers. By means of chromatographic separation, as described in Examples 42 and 44, there were obtained two distinct diastereoisomers having melting point of 211°-214° C. and 175°-178° C. respectively.

Workup

  1. additionAt this temperature, slow dropwise addition
  2. customto return to room temperature
  3. concentrationconcentrated to dryness
  4. dissolutionThe residue was dissolved in ethyl ether
  5. filtrationfiltered
  6. concentrationthe filtrate again concentrated to dryness
  7. customAfter three crystallizations
  8. additionfrom a mixture of isopropanol

Sources & evidence

ORD record
ord-c0d18aeed7bc4518bd70953411d7f51a
Source dataset
uspto-grants-1981_06
Patent number
US04271160

Reaction notes

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