1,1'-Carbonyldiimidazole → ethyl 2-((1R)-1-{2-[(benzyloxy)amino]-2-oxoethyl}-4-cyclohexylbutyl)-1,3-oxazole-4-carboxylate

HRID 1279861Notes

Reaction equation

HRID 1279861 reaction equation
FC(F)(F)C(O)=O.[CH:8]1([CH2:14][CH2:15][CH2:16][C@@H:17]([C:22]2[O:23][CH:24]=[C:25]([C:27]([O:29][CH2:30][CH3:31])=[O:28])[N:26]=2)[CH2:18][C:19]([OH:21])=O)[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1.C(N1C=CN=C1)(N1C=CN=C1)=O.Cl.[CH2:45]([O:52][NH2:53])[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1.C(N(CC)C(C)C)(C)C>O1CCCC1.C(OCC)(=O)C>[CH2:45]([O:52][NH:53][C:19](=[O:21])[CH2:18][C@H:17]([C:22]1[O:23][CH:24]=[C:25]([C:27]([O:29][CH2:30][CH3:31])=[O:28])[N:26]=1)[CH2:16][CH2:15][CH2:14][CH:8]1[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]1)[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1

Participants

7

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 102312Benzyloxyamine hydrochlorideHCID 69778281(3R)-6-Cyclohexyl-3-[4-(ethoxycarbonyl)-1,3-oxazol-2-yl]hexanoic acid trifluoroacetate

Product 1

HCID 60077661ethyl 2-((1R)-1-{2-[(benzyloxy)amino]-2-oxoethyl}-4-cyclohexylbutyl)-1,3-oxazole-4-carboxylateYield 86.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of (3R)-6-cyclohexyl-3-[4-(ethoxycarbonyl)-1,3-oxazol-2-yl]hexanoic acid trifluoroacetate (Preparation 63) (1.66 g, 3.68 mmol), 1,1′-carbonyldiimidazole (0.80 g, 4.93 mmol), O-benzylhydroxylamine hydrochloride (1.57 g, 9.84 mmol) and N,N-diisopropylethylamine (1.71 ml, 9.82 mmol) in anhydrous tetrahydrofuran (10 ml) was stirred at room temperature for 72 hours. The mixture was diluted with ethyl acetate (50 ml) and washed sequentially with a saturated solution of sodium hydrogen carbonate, aqueous citric acid solution (10% w/v) and brine, dried over anhydrous magnesium sulphate, filtered and the solvent removed under reduced pressure. The residue was purified by column chromatography on silica gel eluting with dichloromethane:methanol (98:2) then further purified by column chromatography on silica gel eluting with ethyl acetate:pentane (50:50) to afford the title compound as an orange oil (1.41 g)

Workup

  1. washwashed sequentially with a saturated solution of sodium hydrogen carbonate, aqueous citric acid solution (10% w/v) and brine
  2. dry with materialdried over anhydrous magnesium sulphate
  3. filtrationfiltered
  4. customthe solvent removed under reduced pressure
  5. customThe residue was purified by column chromatography on silica gel eluting with dichloromethane:methanol (98:2)
  6. customthen further purified by column chromatography on silica gel eluting with ethyl acetate:pentane (50:50)

Sources & evidence

ORD record
ord-52d32cd5353d495a8eda5ae5cdb45fe3
Source dataset
uspto-grants-2002_09
Patent number
US06448278B2

Reaction notes

Loading…