Iodine → HCID 178499356, compound

HRID 244897Notes

Reaction equation

HRID 244897 reaction equation
[Li]CCCC.C(NC(C)C)(C)C.[CH3:13][O:14][C:15]([C:17]1[S:18][CH:19]=[CH:20][C:21]=1[N:22]([CH:32]1[CH2:41][CH2:40][C:35]2([O:39][CH2:38][CH2:37][O:36]2)[CH2:34][CH2:33]1)[C:23]([C@H:25]1[CH2:30][CH2:29][C@H:28]([CH3:31])[CH2:27][CH2:26]1)=[O:24])=[O:16].[I:42]I.[NH4+].[Cl-]>C1COCC1.C(OCC)(=O)C.O>[CH3:13][O:14][C:15]([C:17]1[S:18][C:19]([I:42])=[CH:20][C:21]=1[N:22]([CH:32]1[CH2:41][CH2:40][C:35]2([O:39][CH2:38][CH2:37][O:36]2)[CH2:34][CH2:33]1)[C:23]([C@H:25]1[CH2:26][CH2:27][C@H:28]([CH3:31])[CH2:29][CH2:30]1)=[O:24])=[O:16]

Participants

9

Reactant 5

HCID 807IodineHCID 7912DiisopropylamineHCID 25517Ammonium ChlorideHCID 178418339ButyllithiumHCID 178499312HCID 178499312, compound

Product 1

HCID 178499356HCID 178499356, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

n-BuLi (2 eq.) is added dropwise for 10 min to a cold (−40° C.) solution of diisopropylamine (1 eq.) in dry THF. The reaction mixture is stirred at the same temperature for 30 min. Then a solution of 3-[(1,4-dioxa-spiro[4.5]dec-8-yl)-(trans-4-methyl-cyclohexane-carbonyl)-amino]-thiophene-2-carboxylic acid methyl ester (1 eq.) in THF is added dropwise (35 min) keeping the internal temperature around −40° C. The reaction mixture is stirred for 30 min and a solution of iodine (2 eq.) in THF is added dropwise, stirred for 30 min at the same temperature before being added a sat. solution of NH4Cl. The reaction mixture is diluted with ethyl acetate and water. The organic layer is separated and washed with 5% sodium thiosulfate solution. The organic layer is separated, dried (Na2SO4) and evaporated to a suspension and then added heptane. The suspension is stirred at 0° C. for 30 min, filtered and washed with heptane to obtain 3-[(1,4-dioxa-spiro[4.5]dec-8-yl)-(trans-4-methyl-cyclo-hexanecarbonyl)-amino]-5-iodo-thiophene-2-carboxylic acid methyl ester.

Workup

  1. customthe internal temperature around −40° C
  2. stirringThe reaction mixture is stirred for 30 min
  3. stirringstirred for 30 min at the same temperature
  4. customThe organic layer is separated
  5. washwashed with 5% sodium thiosulfate solution
  6. customThe organic layer is separated
  7. dry with materialdried (Na2SO4)
  8. customevaporated to a suspension
  9. stirringThe suspension is stirred at 0° C. for 30 min
  10. filtrationfiltered
  11. washwashed with heptane

Sources & evidence

ORD record
ord-d97aca49a8dc42ca85969b3dd93ac11f
Source dataset
uspto-grants-2014_02
Patent number
US08658674B2

Reaction notes

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