Diethyl Ether → N-[2-Hydroxy-5-[1-hydroxy-2-[[6-[4-[(2-naphthalenyl)oxy]butoxy]hexyl]amino]ethyl]phenyl]methanesulphonamide

HRID 2372569Notes

Reaction equation

HRID 2372569 reaction equation
Br[CH2:2][C:3]([C:5]1[CH:6]=[CH:7][C:8]([O:16]CC2C=CC=CC=2)=[C:9]([NH:11][S:12]([CH3:15])(=[O:14])=[O:13])[CH:10]=1)=[O:4].[CH:24]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH:27]=[CH:26][C:25]=1[O:34][CH2:35][CH2:36][CH2:37][CH2:38][O:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][NH:46]CC1C=CC=CC=1.[BH4-].[Na+].C(OCC)C>ClCCl.CO.O>[OH:16][C:8]1[CH:7]=[CH:6][C:5]([CH:3]([OH:4])[CH2:2][NH:46][CH2:45][CH2:44][CH2:43][CH2:42][CH2:41][CH2:40][O:39][CH2:38][CH2:37][CH2:36][CH2:35][O:34][C:25]2[CH:26]=[CH:27][C:28]3[C:33](=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH:24]=2)=[CH:10][C:9]=1[NH:11][S:12]([CH3:15])(=[O:13])=[O:14]

Participants

8

Reactant 4

HCID 3283Diethyl EtherHCID 4311764Sodium borohydrideHCID 11200351N-[2-(benzyloxy)-5-(2-bromoacetyl)phenyl]methanesulfonamideHCID 19101826N-[6-[4-[(2-Naphthalenyl)oxy]butoxy]hexyl]benzenemethanamine

Product 1

HCID 19101841N-[2-Hydroxy-5-[1-hydroxy-2-[[6-[4-[(2-naphthalenyl)oxy]butoxy]hexyl]amino]ethyl]phenyl]methanesulphonamideYield 45.9%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent2×

Procedure

A solution of N-[5-(bromoacetyl)-2-(phenylmethoxy)phenyl]methanesulphonamide (1.96 g), N-[6-[4-[(2-naphthalenyl)oxy]butoxy]hexyl]benzenemethanamine (2.0 g) and DEA (0.96 g) in dichloromethane (45 ml) was stirred under nitrogen at room temperature for 22 h. The mixture was treated with water (100 ml) and extracted with dichloromethane (2×150 ml). The combined organic extracts were dried and evaporated in vacuo to give an oil which was dissolved in methanol (30 ml) and dichloromethane (20 ml) and cooled to 0°-5° C. under nitrogen. Sodium borohydride (0.50 g) was added portionwise and the solution stirred at room temperature for 30 min, then carefully diluted with water (20 ml). The solvent was evaporated in vacuo, the residue partitioned between water (100 ml) and dichloromethane (150 ml) and the aqueous phase re-extracted with dichloromethane (150 ml), the combined organic extracts being dried and evaporated in vacuo to give an oil which was purified by FCC eluting with System C (95:5:1). A solution of the oil (3.41 g) in absolute ethanol (60 ml) was hydrogenated over pre-reduced 10% palladium on charcoal catalyst (50% aqueous paste, 1.5 g) in absolute ethanol (10 ml) for 4.5 h. The mixture was filtered through hyflo and evaporated in vacuo to give an oil which was purified by FCC eluting with System B (40:10:1) to give a cream solid. Trituration with diethyl ether gave the title compound as a white solid (1.23 g), m.p. 99.5°-100.5°.

Workup

  1. extractionextracted with dichloromethane (2×150 ml)
  2. customThe combined organic extracts were dried
  3. customevaporated in vacuo
  4. customto give an oil which
  5. customThe solvent was evaporated in vacuo
  6. customthe residue partitioned between water (100 ml) and dichloromethane (150 ml)
  7. extractionthe aqueous phase re-extracted with dichloromethane (150 ml)
  8. customthe combined organic extracts being dried
  9. customevaporated in vacuo
  10. customto give an oil which
  11. customwas purified by FCC
  12. washeluting with System C (95:5:1)
  13. waitA solution of the oil (3.41 g) in absolute ethanol (60 ml) was hydrogenated over pre-reduced 10% palladium on charcoal catalyst (50% aqueous paste, 1.5 g) in absolute ethanol (10 ml) for 4.5 h
  14. filtrationThe mixture was filtered through hyflo
  15. customevaporated in vacuo
  16. customto give an oil which
  17. customwas purified by FCC
  18. washeluting with System B (40:10:1)
  19. customto give a cream solid

Sources & evidence

ORD record
ord-46b0137b10cc49f28511ef25ccc4ea4b
Source dataset
uspto-grants-1992_03
Patent number
US05099068

Reaction notes

Loading…