1,4-Dioxane → ((S)-1-{(S)-8-[4-(4-Bromo-phenyl)-1H-imidazol-2-yl]-1,4-dioxa-7-aza-spiro[4.4]nonane-7-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester

HRID 709365Notes

Reaction equation

HRID 709365 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)[CH2:9][NH:10][C:11]([C@@H:13]2[CH2:21][C:16]3([O:20][CH2:19][CH2:18][O:17]3)[CH2:15][N:14]2[C:22](=[O:32])[C@@H:23]([NH:27][C:28](=[O:31])[O:29][CH3:30])[CH:24]([CH3:26])[CH3:25])=O)=[CH:4][CH:3]=1.O1CCOCC1.C([O-])(=O)C.[NH4+:44]>CCOC(C)=O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:44][C:11]([C@@H:13]3[CH2:21][C:16]4([O:17][CH2:18][CH2:19][O:20]4)[CH2:15][N:14]3[C:22](=[O:32])[C@@H:23]([NH:27][C:28](=[O:31])[O:29][CH3:30])[CH:24]([CH3:26])[CH3:25])=[N:10][CH:9]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 312751,4-DioxaneHCID 517165Ammonium AcetateHCID 86670838HCID 86670838, compound

Product 1

HCID 59610362((S)-1-{(S)-8-[4-(4-Bromo-phenyl)-1H-imidazol-2-yl]-1,4-dioxa-7-aza-spiro[4.4]nonane-7-carbonyl}-2-methyl-propyl)-carbamic acid methyl esterYield 97.2%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

In a 5 mL seal tube, methyl (S)-1-((S)-8-(2-(4-bromophenyl)-2-oxoethylcarbamoyl)-1,4-dioxa-7-azaspiro[4.4]nonan-7-yl)-3-methyl-1-oxobutan-2-ylcarbamate (75 mg, 142 μmol) was combined with 1,4-dioxane (2 ml) to give a light yellow solution. Ammonium acetate (110 mg, 1.42 mmol) was added and it was stirred at 110° C. overnight. It was cooled and diluted with EtOAc(10 ml), filtered and concentrated in vacuo to afford methyl (S)-1-((S)-8-(5-(4-bromophenyl)-1H-imidazol-2-yl)-1,4-dioxa-7-azaspiro[4.4]nonan-7-yl)-3-methyl-1-oxobutan-2-ylcarbamate as a light brownish solid (70 mg, 96.8%). ESI-LRMS m/e calcd for C22H27BrN4O5 [M+] 507. found 508 [M+H+].

Workup

  1. customIn a 5 mL seal tube
  2. customto give a light yellow solution
  3. temperatureIt was cooled
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a08fe1b3eab94a6ebb7f595c56b1fcc6
Source dataset
uspto-grants-2015_11
Patent number
US09180193B2

Reaction notes

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