Iodine → HCID 59146064, compound

HRID 1512827Notes

Reaction equation

HRID 1512827 reaction equation
[BH4-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]([C:14]2[O:18][N:17]=[C:16]([C:19]3[CH:20]=[CH:21][CH:22]=[C:23]4[C:27]=3[N:26]([CH3:28])[CH:25]=[C:24]4[CH2:29][CH2:30][C:31](O)=[O:32])[N:15]=2)[CH:7]=[CH:8][C:9]=1[O:10][CH:11]([CH3:13])[CH3:12].II>C1COCC1>[Cl:3][C:4]1[CH:5]=[C:6]([C:14]2[O:18][N:17]=[C:16]([C:19]3[CH:20]=[CH:21][CH:22]=[C:23]4[C:27]=3[N:26]([CH3:28])[CH:25]=[C:24]4[CH2:29][CH2:30][CH2:31][OH:32])[N:15]=2)[CH:7]=[CH:8][C:9]=1[O:10][CH:11]([CH3:12])[CH3:13]

Participants

5

Reactant 3

HCID 807IodineHCID 4311764Sodium borohydrideHCID 44547316HCID 44547316, compound

Product 1

HCID 59146064HCID 59146064, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a suspension of NaBH4 (0.52 g) in THF (50 mL) was added a solution of 3-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]propanoic acid (E2) (1.5 g) in THF (20 mL) dropwise. The mixture was stirred for 15 mins and a solution of I2 (1.7 g) in THF (90 mL) was added dropwise. The reaction mixture was stirred at 20° C. for 20 h. The reaction mixture was quenched with water, the solvent was evaporated and the residue was partitioned between ethyl acetate (100 mL) and water (50 mL). The organic phase was washed with aqueous HCl (2 M), water and brine, dried over sodium sulphate and evaporated to give the crude product as yellow foam, which was purified by column chromatography (15% EtOAc in hexanes) to afford 3-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]-1-propanol (D128) (900 mg). δH (DMSO-d6, 400 MHz): 1.35 (6H, d), 1.80 (2H, m), 2.75 (2H, t), 3.48 (2H, t), 3.60 (3H, s), 4.47 (1H, t), 4.88 (1H, m), 7.16 (2H, m), 7.43 (2H, m), 7.77 (1H, d), 8.12 (1H, dd), 8.19 (1H, d). MS (ES): C23H24ClN3O3 requires 425; found 426.2 (M+H+).

Workup

  1. stirringThe reaction mixture was stirred at 20° C. for 20 h
  2. customThe reaction mixture was quenched with water
  3. customthe solvent was evaporated
  4. customthe residue was partitioned between ethyl acetate (100 mL) and water (50 mL)
  5. washThe organic phase was washed with aqueous HCl (2 M), water and brine
  6. dry with materialdried over sodium sulphate
  7. customevaporated
  8. customto give the crude product as yellow foam, which
  9. customwas purified by column chromatography (15% EtOAc in hexanes)

Sources & evidence

ORD record
ord-84ea2c406c0f47cf8c9638594ff154e2
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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