Sodium borohydride → (Z)-N-[5-[1-Hydroxy-2-[[6-[3-(6-methoxy-2-naphthalenyl)-2-propenyloxy]hexyl](phenylmethyl)amino]ethyl]-2-(phenylmethoxy)phenyl]methanesulphonamide

HRID 358919Notes

Reaction equation

HRID 358919 reaction equation
Br[CH2:2][C:3]([C:5]1[CH:6]=[CH:7][C:8]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[C:9]([NH:11][S:12]([CH3:15])(=[O:14])=[O:13])[CH:10]=1)=[O:4].[CH3:24][O:25][C:26]1[CH:27]=[C:28]2[C:33](=[CH:34][CH:35]=1)[CH:32]=[C:31]([C:36]#[C:37][CH2:38][O:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][NH:46][CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)[CH:30]=[CH:29]2.[BH4-].[Na+]>ClCCl.O.CO>[OH:4][CH:3]([C:5]1[CH:6]=[CH:7][C:8]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[C:9]([NH:11][S:12]([CH3:15])(=[O:14])=[O:13])[CH:10]=1)[CH2:2][N:46]([CH2:45][CH2:44][CH2:43][CH2:42][CH2:41][CH2:40][O:39][CH2:38]/[CH:37]=[CH:36]\[C:31]1[CH:30]=[CH:29][C:28]2[C:33](=[CH:34][CH:35]=[C:26]([O:25][CH3:24])[CH:27]=2)[CH:32]=1)[CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1

Participants

7

Reactant 3

HCID 4311764Sodium borohydride2×HCID 11200351N-[2-(benzyloxy)-5-(2-bromoacetyl)phenyl]methanesulfonamideHCID 19101827N-[6-[3-(6-methoxy-2-naphthalenyl)-2-propynyloxy]hexyl]benzenemethanamine

Product 1

HCID 67824901(Z)-N-[5-[1-Hydroxy-2-[[6-[3-(6-methoxy-2-naphthalenyl)-2-propenyloxy]hexyl](phenylmethyl)amino]ethyl]-2-(phenylmethoxy)phenyl]methanesulphonamideYield 44.2%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent2×

Procedure

A solution of N-[5-(bromoacetyl)-2-(phenylmethoxy)phenyl]methanesulphonamide (0.96 g), N-[6-[3-(6-methoxy-2-naphthalenyl)-2-propynyloxy]hexyl]benzenemethanamine (1.38 g) and DEA (0.47 g) in dichloromethane (22 ml) was stirred at room temperature under nitrogen for 22 h, diluted with water (100 ml) and extracted with dichloromethane (2×100 ml). The combined organic extracts were dried and evaporated in vacuo to give an oil. The oil was dissolved in methanol (20 ml) and dichloromethane (20 ml) and sodium borohydride (0.25 g) were added portionwise to the solution at 0° C. under nitrogen. The solution was stirred at room temperature for 1 h, cooled to 0° C. and a further portion of sodium borohydride (0.1 g) added. The solution was stirred at room temperature for 30 min and then carefully diluted with water (10 ml) and evaporated in vacuo. The residue was partitioned between dichloromethane (100 ml) and water (100 ml). The aqueous phase was re-extracted with dichloromethane (100 ml) and the combined organic fractions dried and evaporated in vacuo to give an oil. Purification by FCC eluting with System C (100:2:1) gave the title compound as a colourless oil (0.77 g), t.l.c. (System C 98:2:1) Rf 0.23.

Workup

  1. extractionextracted with dichloromethane (2×100 ml)
  2. customThe combined organic extracts were dried
  3. customevaporated in vacuo
  4. customto give an oil
  5. temperaturecooled to 0° C.
  6. stirringThe solution was stirred at room temperature for 30 min
  7. customevaporated in vacuo
  8. customThe residue was partitioned between dichloromethane (100 ml) and water (100 ml)
  9. extractionThe aqueous phase was re-extracted with dichloromethane (100 ml)
  10. customthe combined organic fractions dried
  11. customevaporated in vacuo
  12. customto give an oil
  13. customPurification by FCC
  14. washeluting with System C (100:2:1)

Sources & evidence

ORD record
ord-e7e6b43cadc74733845974b581b7062f
Source dataset
uspto-grants-1991_03
Patent number
US04997986

Reaction notes

Loading…