Propanal → HCID 10224846, compound

HRID 857355Notes

Reaction equation

HRID 857355 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]CCCC.CCCCCC.[CH:41](=[O:44])[CH2:42][CH3:43]>C1COCC1>[Cl:26][C:23]1[CH:24]=[CH:25][C:20]([S:19][C:4]2[C:3]3[C:2]([CH:41]([OH:44])[CH2:42][CH3:43])=[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

7

Reactant 5

HCID 527PropanalHCID 8058HexaneHCID 10226143HCID 10226143, compoundHCID 178418339ButyllithiumHCID 178418689HCID 178418689, compound

Product 1

HCID 10224846HCID 10224846, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

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 7A, 700 mg, 1.5 mmol) in THF (15 mL) at −78° C. was added 3M MeMgBr in THF (1.9 mmol) followed by the addition of 1.6M nBuLi in hexane (3.1 mmol). The reaction mixture was stirred at −78° C. for 2 minutes and an excess of propionaldehyde was added. The reaction mixture was stirred at −78° C. for 15 minutes, warmed to r.t 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 silica gel chromatography eluted with EtOAc/hexanes/AcOH (20:30:1) to provide the title compound as a white solid.

Workup

  1. stirringThe reaction mixture was stirred at −78° C. for 15 minutes
  2. temperaturewarmed
  3. customquenched with saturated aqueous NH4Cl The phases
  4. customwere separated
  5. extractionthe aqueous layer was extracted with EtOAc
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel chromatography
  9. washeluted with EtOAc/hexanes/AcOH (20:30:1)

Sources & evidence

ORD record
ord-68f0ab88593d451ba87d45198e6b7a55
Source dataset
uspto-grants-2006_12
Patent number
US07144913B2

Reaction notes

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