Isopropanol → N-Cyclohexyl-N'-(3-{[2-({6-[(5R)-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-oxo-1,3-oxazolidin-3-yl]hexyl}oxy)ethoxy]methyl}phenyl)urea

HRID 219012Notes

Reaction equation

HRID 219012 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:34]=[CH:35][CH:36]=1)[CH2:5][O:6][CH2:7][CH2:8][O:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][N:16]1[CH2:20][C@@H:19]([C:21]2[CH:32]=[CH:31][C:24]3[O:25][C:26]([CH3:30])([CH3:29])[O:27][CH2:28][C:23]=3[CH:22]=2)[O:18][C:17]1=[O:33].[CH:37]1([N:43]=[C:44]=[O:45])[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]1.C(O)(C)C>ClCCl>[CH:37]1([NH:43][C:44]([NH:1][C:2]2[CH:36]=[CH:35][CH:34]=[C:4]([CH2:5][O:6][CH2:7][CH2:8][O:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][N:16]3[CH2:20][C@@H:19]([C:21]4[CH:32]=[CH:31][C:24]5[O:25][C:26]([CH3:30])([CH3:29])[O:27][CH2:28][C:23]=5[CH:22]=4)[O:18][C:17]3=[O:33])[CH:3]=2)=[O:45])[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]1

Participants

5

Reactant 3

HCID 3776IsopropanolHCID 18502Cyclohexyl isocyanate2×HCID 46833388(5R)-3-{6-[2-{[(3-aminophenyl)methyl]oxy}ethoxy]hexyl}-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-one

Product 1

HCID 66845105N-Cyclohexyl-N'-(3-{[2-({6-[(5R)-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-oxo-1,3-oxazolidin-3-yl]hexyl}oxy)ethoxy]methyl}phenyl)ureaYield 81.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
20 °C

Procedure

A solution of (5R)-3-(6-{2-[(3-aminobenzyl)oxy]ethoxy}hexyl)-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-one (0.209 g) in dichloromethane (4 ml) was treated with cyclohexyl isocyanate (0.075 g) and the mixture stirred under nitrogen at 20° C. for 3 h. At this point further cyclohexyl isocyanate (0.150 g) was added, and the reaction mixture stirred for a further 65 h. Isopropanol (15 ml) was added to quench excess isocyanate, and the mixture stirred for 3 h. The solvents were removed in vacuo to give a residue which was purified by Biotage. Elution with 6:4 EtOAc/cyclohexane followed by solvent evaporation in vacuo gave the title compound (0.212 g). LCMS RT=3.77 min, ES+ve 624 (MH)+.

Workup

  1. stirringthe reaction mixture stirred for a further 65 h
  2. customto quench excess isocyanate
  3. stirringthe mixture stirred for 3 h
  4. customThe solvents were removed in vacuo
  5. customto give a residue which
  6. customwas purified by Biotage
  7. washElution with 6:4 EtOAc/cyclohexane
  8. customfollowed by solvent evaporation in vacuo

Sources & evidence

ORD record
ord-e295a49a91b2425299a6e77aa529f645
Source dataset
uspto-grants-2012_06
Patent number
US08198483B2

Reaction notes

Loading…