Iodine → HCID 178499357, compound

HRID 749385Notes

Reaction equation

HRID 749385 reaction equation
C(NC(C)C)(C)C.C([Mg]Cl)CCC.[CH3:14][O:15][C:16]([C:18]1[S:19][CH:20]=[CH:21][C:22]=1[N:23]([C:31]([C@H:33]1[CH2:38][CH2:37][C@H:36]([CH3:39])[CH2:35][CH2:34]1)=[O:32])[CH:24]1[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]1)=[O:17].[I:40]I>C1COCC1>[CH3:14][O:15][C:16]([C:18]1[S:19][C:20]([I:40])=[CH:21][C:22]=1[N:23]([C:31]([C@H:33]1[CH2:34][CH2:35][C@H:36]([CH3:39])[CH2:37][CH2:38]1)=[O:32])[CH:24]1[CH2:25][CH2:26][N:27]([CH3:30])[CH2:28][CH2:29]1)=[O:17]

Participants

6

Reactant 4

HCID 807IodineHCID 7912DiisopropylamineHCID 178418265HCID 178418265, compoundHCID 178499314HCID 178499314, compound

Product 1

HCID 178499357HCID 178499357, compoundYield 99.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a stirred solution of diisopropyl amine (0.3 mL, 2.14 mmol) in THF (10 mL) was added n-BuMgCl (2.0 M in ether, 1.0 mL, 2.0 mol), stirred for 24 h. To the resultant solution was added drop wise a solution of 3-[(trans-4-methyl-cyclohexanecarbonyl)-(1-methyl-piperidin-4-yl)-amino]-thiophene-2-carboxylic acid methyl ester (0.189 g, 0.5 mmol) in THF (2.0 mL), stirred for 1 h at room temperature. It was then added a solution of Iodine (1.28 g, 5.0 mmol) in THF (2.0 mL), stirred for 1 h. Reaction mixture was then quenched with 10% aq Na2S2O3 solution, extracted with EtOAc, washed with brine, dried, and concentrated. Purification of the residue on small plug of silica gel bond elute using DCM/CHCl3/MeOH/Et3N (200:90:16:1) as eluent gave 5-iodo-3-[(trans-4-methyl-cyclohexanecarbonyl)-(1-methyl-piperidin-4-yl)-amino]-thiophene-2-carboxylic acid methyl ester (0.250 g, quantitative). NMR 1H (CDCl3, 400 MHz): 7.05 (s, 1H), 4.68-4.55 (m, 1H), 3.83 (s, 3H), 2.95-2.8 (m, 2H), 2.26 (s, 3H), 2.2-1.1 (m, 14 H), 0.819 (d, J=6.3, 3H), 0.75-0.6 (m, 2H).

Workup

  1. stirringstirred for 1 h at room temperature
  2. stirringstirred for 1 h
  3. customReaction mixture
  4. customwas then quenched with 10% aq Na2S2O3 solution
  5. extractionextracted with EtOAc
  6. washwashed with brine
  7. customdried
  8. concentrationconcentrated
  9. customPurification of the residue on small plug of silica gel bond
  10. washelute

Sources & evidence

ORD record
ord-9631523af3e8434a8aecacb3e9551e03
Source dataset
uspto-grants-2008_07
Patent number
US07402608B2

Reaction notes

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