Isobutyraldehyde → HCID 10204113, compound

HRID 857350Notes

Reaction equation

HRID 857350 reaction equation
Br[C:2]1[C:3]2[C:4]([S:19][C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)=[C:5]3[CH:14]([CH2:15][C:16]([OH:18])=[O:17])[CH2:13][CH2:12][N:6]3[C:7]=2[CH:8]=[C:9]([F:11])[CH:10]=1.C[Mg+].[Br-].[Li]C(CC)C.[CH:35](=[O:39])[CH:36]([CH3:38])[CH3:37]>C1COCC1>[Cl:26][C:23]1[CH:24]=[CH:25][C:20]([S:19][C:4]2[C:3]3[C:2]([CH:35]([OH:39])[CH:36]([CH3:38])[CH3:37])=[CH:10][C:9]([F:11])=[CH:8][C:7]=3[N:6]3[CH2:12][CH2:13][CH:14]([CH2:15][C:16]([OH:18])=[O:17])[C:5]=23)=[CH:21][CH:22]=1

Participants

6

Reactant 4

HCID 6561IsobutyraldehydeHCID 10226143HCID 10226143, compoundHCID 178418400CID 53628100HCID 178418689HCID 178418689, compound

Product 1

HCID 10204113HCID 10204113, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of (+/−)-[8-bromo-9-[(4-chlorophenyl)sulfanyl]-6-fluoro-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl]acetic acid (Example 7, 100 mg, 0.22 mmol) in THF (4 mL) at −78° C. was added 3M MeMgBr (0.26 mmol) followed by the addition of 1.3M sec-BuLi (0.31 mmol). The reaction mixture was stirred at −78° C. for 20 minutes and an excess of isobutyraldehyde was added. The reaction mixture was slowly warmed to −20° C. over a 30 minute period and quenched with saturated aqueous NH4Cl. The phases were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were dried over Na2SO4 and concentrated. The residue was purified by preparative HPLC using a Zorbax column eluted with 10% iPrOH in Hexanes containing 0.2% of AcOH to provide 40 mg of the title compound as a white solid.

Workup

  1. temperatureThe reaction mixture was slowly warmed to −20° C. over a 30 minute period
  2. customquenched with saturated aqueous NH4Cl
  3. customThe phases were separated
  4. extractionthe aqueous layer was extracted with EtOAc
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. concentrationconcentrated
  7. customThe residue was purified by preparative HPLC
  8. washeluted with 10% iPrOH in Hexanes containing 0.2% of AcOH

Sources & evidence

ORD record
ord-3dcd03818e2d49408ebc27447e9f105e
Source dataset
uspto-grants-2006_12
Patent number
US07144913B2

Reaction notes

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