2-(6-Methoxy-2-naphthyl)propionic acid → 4-[2-(6-Methoxynaphthalen-2-yl)propyl]thiomorpholine

HRID 1389049Notes

Reaction equation

HRID 1389049 reaction equation
C(Cl)(=O)C(Cl)=O.[CH3:7][O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[CH:15]=[C:14]([CH:19]([CH3:23])[C:20](O)=O)[CH:13]=[CH:12]2.Cl.[NH:25]1[CH2:30][CH2:29][S:28][CH2:27][CH2:26]1.C(N1CCOCC1)C.B>C1C=CC=CC=1.C(Cl)Cl.O1CCCC1.O>[N:25]1([CH2:20][CH:19]([C:14]2[CH:13]=[CH:12][C:11]3[C:16](=[CH:17][CH:18]=[C:9]([O:8][CH3:7])[CH:10]=3)[CH:15]=2)[CH3:23])[CH2:30][CH2:29][S:28][CH2:27][CH2:26]1

Participants

10

Reactant 5

HCID 13022-(6-Methoxy-2-naphthyl)propionic acidHCID 6331BoraneHCID 7525EthylmorpholineHCID 65578Oxalyl chlorideHCID 3014410Thiomorpholine hydrochloride

Product 1

HCID 30553004-[2-(6-Methoxynaphthalen-2-yl)propyl]thiomorpholine

Reagents, catalysts & solvents 4

HCID 241BenzeneSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Oxalyl chloride (10 ml) is added dropwise to a suspension of 2-(6-methoxynaphth-2-yl)-propionic acid (17.4 g, 75.6 mmols) in benzene (200 ml). After refluxing for 2 hours, the benzene is evaporated off under reduced pressure and the residue is taken up in alcohol-free methylene chloride (100 ml). This solution is added dropwise, in the course of 30 minutes, to a cooled suspension (0° C.) of thiamorpholine hydrochloride (11.6 g, 83.16 mmols) and N-ethylmorpholine (19.12 g, 166 mmols) in methylene chloride (100 ml). After standing overnight, the reaction medium is washed successively with water, hydrochloric acid (10% strength), water, aqueous sodium bicarbonate solution (saturated) and water and then dried (Na2SO4) and evaporated. This yields a solid which is the intermediate (IV). A solution of this amide (5.60 g, 17.78 mmols) in tetrahydrofuran (50 ml) is added dropwise to a stirred solution of borane (55 mmols) in tetrahydrofuran (50 ml), which has been cooled to 0° C. The solution is then heated at the reflux temperature for 2 hours and again cooled to 0° C. Water is then added cautiously in order to destroy the excess borane, and dilute hydrochloric acid is added.

Workup

  1. temperatureAfter refluxing for 2 hours
  2. customthe benzene is evaporated off under reduced pressure
  3. washthe reaction medium is washed successively with water, hydrochloric acid (10% strength), water, aqueous sodium bicarbonate solution (saturated) and water
  4. dry with materialdried (Na2SO4)
  5. customevaporated
  6. customThis yields a solid which
  7. temperatureThe solution is then heated at the reflux temperature for 2 hours
  8. temperatureagain cooled to 0° C
  9. customto destroy the excess borane, and dilute hydrochloric acid
  10. additionis added

Sources & evidence

ORD record
ord-f045847b9a1a4321b72b0d41b1b33894
Source dataset
uspto-grants-1981_01
Patent number
US04243665

Reaction notes

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