Hydrochloric Acid → HCID 10317953, compound

HRID 2055728Notes

Reaction equation

HRID 2055728 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7]([CH3:12])=[C:6]2[C:13]([CH3:18])([CH3:17])[C:14]([OH:16])=[O:15].C[Si]([N-][Si](C)(C)C)(C)C.[K+].[Cl:29][C:30]1[CH:38]=[CH:37][C:33]([C:34](Cl)=[O:35])=[CH:32][CH:31]=1.[NH4+].[Cl-].Cl>C1COCC1>[Cl:29][C:30]1[CH:38]=[CH:37][C:33]([C:34]([N:8]2[C:9]3[C:5](=[CH:4][C:3]([O:2][CH3:1])=[CH:11][CH:10]=3)[C:6]([C:13]([CH3:18])([CH3:17])[C:14]([OH:16])=[O:15])=[C:7]2[CH3:12])=[O:35])=[CH:32][CH:31]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 85014-Chlorobenzoyl chlorideHCID 25517Ammonium ChlorideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 69317471HCID 69317471, compound

Product 1

HCID 10317953HCID 10317953, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To an ice-cooled solution of 2-(5-methoxy-2-methyl-1H-indol-3-yl)-2-methyl-propionic acid (150 mg, 0.611 mmol) in THF (4 mL) was added KHMDS (0.5M solution in toluene; 3.1 mL, 1.55 mmol) and the solution stirred for 20 min at 0° C. 4-Chlorobenzoyl chloride (85.4 uL, 0.672 mmol) was added and the solution allowed to attain ambient temperature. After 30 minutes, satd. aq. NH4Cl soln. was added and the aqueous layer acidified with dil. HCl, extracted with EtOAc, the organic phase dried (MgSO4), filtered and evaporated. The residue was purified by column chromatography (0 to 30% acetone:hexanes) to afford 2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]-2-methyl-propionic acid as an orange foam. 1H NMR (500 MHz, CDCl3) δ 7.69 (2H, d, J=8.4 Hz), 7.46 (2H, d, J=8.4 Hz), 7.08 (1H, d, J=2.4 Hz), 6.91 (1H, d, J=9.0 Hz), 6.66 (1H, dd, J=9.0, 2.4 Hz), 3.74 (3H, s), 2.39 (3H, s), 1.79 (6H, s). LCMS(EI) 386 (M+H)+.

Workup

  1. customto attain ambient temperature
  2. waitAfter 30 minutes
  3. additionwas added
  4. extractionextracted with EtOAc
  5. dry with materialthe organic phase dried (MgSO4)
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by column chromatography (0 to 30% acetone:hexanes)

Sources & evidence

ORD record
ord-0efcf10fdcf648c2bd13d07bd06b3c1d
Source dataset
uspto-grants-2008_02
Patent number
US07332516B2

Reaction notes

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