HCID 86614051, compound → HCID 86614050, compound

HRID 1727173Notes

Reaction equation

HRID 1727173 reaction equation
[Cl:1][C:2]1[C:11]2[N:10]([CH3:12])[O:9][C@H:8]3[NH:13][C@H:14]([C:16]([O:18][C@@H:19]4[C@:28]5([OH:29])[C@H:23]([C@@H:24]([C:31]([CH3:33])=[CH2:32])[CH2:25][CH2:26][C@H:27]5[CH3:30])[CH:22]=[C:21]([CH3:34])[C@H:20]4[O:35][C:36]([NH:38][C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=4)=[O:37])=[O:17])[CH2:15][C@@:7]3([OH:45])[C:6]=2[CH:5]=[CH:4][CH:3]=1.[H][H]>C(OCC)(=O)C.[Pt](=O)=O>[Cl:1][C:2]1[C:11]2[N:10]([CH3:12])[O:9][C@H:8]3[NH:13][C@H:14]([C:16]([O:18][C@@H:19]4[C@:28]5([OH:29])[C@@H:23]([C@H:24]([CH:31]([CH3:33])[CH3:32])[CH2:25][CH2:26][C@H:27]5[CH3:30])[CH:22]=[C:21]([CH3:34])[C@H:20]4[O:35][C:36]([NH:38][C:39]4[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=4)=[O:37])=[O:17])[CH2:15][C@@:7]3([OH:45])[C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 86614051HCID 86614051, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 86614050HCID 86614050, compoundYield 19%

Reagents, catalysts & solvents 2

HCID 345198Adams' catalystCatalystHCID 8857Ethyl AcetateSolvent

Procedure

To (1S,2R,4aR,8R,8aR)-8a-hydroxy-2-[(1H-imidazol-1-ylcarbonyl)oxy]-3,8-dimethyl-5-(1-methylethenyl)-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl (2S,3aR,9bR)-6-chloro-9b-hydroxy-5-methyl-1,2,3,3a,5,9b-hexahydropyrrolo[2,3-c][2,1]benzoxazine-2-carboxylate (Preparation 142, 510 mg, 0.83 mmol) in anhydrous pyridine (10 ml) was added aniline hydrochloride (500 mg, 3.8 mmol) and 4-dimethylaminopyridine (240 mg, 2.0 mmol). The reaction mixture was stirred at room temperature under nitrogen for 4 days before pouring into dichloromethane (100 ml) and washing with saturated aqueous citric acid solution (2×50 ml). The organic fraction was dried (Na2SO4) and concentrated in vacuo to give a yellowish solid (490 mg, 93%). The crude product was purified by flash column chromatography on silica gel eluting with a hexane:ethyl acetate gradient (1:1 to 1:5). The pure fractions were collected and concentrated in vacuo to give (1S,2R,4aS,5S,8R,8aR)-8a-hydroxy-3,8-dimethyl-5-(1-methylethenyl)-2-{[(phenylamino)carbonyl]oxy}-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl (2S,3aR,9bR)-6-chloro-9b-hydroxy-5-methyl-1,2,3,3a,5,9b-hexahydropyrrolo[2,3-c][2,1]benzoxazine-2-carboxylate (440 mg, 83%). To a solution of the (1S,2R,4aS,5S,8R,8aR)-8a-hydroxy-3,8-dimethyl-5-(1-methylethenyl)-2-{[(phenylamino)carbonyl]oxy}-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl (2S,3aR,9bR)-6-chloro-9b-hydroxy-5-methyl-1,2,3,3a,5,9b-hexahydropyrrolo[2,3-c][2,1]benzoxazine-2-carboxylate (100 mg, 0.157 mmol) in ethyl acetate (30 ml) was added platinum(IV) oxide (10 mg, 0.044 mmol) and the resulting mixture was hydrogenated at room temperature under 60 psi hydrogen for 10 hours. The reaction mixture was filtered and the filtrate concentrated in vacuo. The crude product, was purified by flash column chromatography on silica gel eluting with hexane ethyl acetate (1:1). The product was further purified to give the title product (19 mg, 19%).

Workup

  1. filtrationThe reaction mixture was filtered
  2. concentrationthe filtrate concentrated in vacuo
  3. customThe crude product, was purified by flash column chromatography on silica gel eluting with hexane ethyl acetate (1:1)
  4. customThe product was further purified

Sources & evidence

ORD record
ord-e24ba21a2c104ba29ab830e3e504e930
Source dataset
uspto-grants-2009_02
Patent number
US07494992B2

Reaction notes

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