5-chloro-N-methoxy-N-methyl-1H-indole-2-carboxamide → 1-(5-chloro-1H-indol-2-yl)pentan-1-one

HRID 1818620Notes

Reaction equation

HRID 1818620 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11](N(OC)C)=[O:12])=[CH:5]2.[Li][CH2:18][CH2:19][CH2:20][CH3:21]>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11](=[O:12])[CH2:18][CH2:19][CH2:20][CH3:21])=[CH:5]2

Participants

4

Reactant 2

HCID 230033115-chloro-N-methoxy-N-methyl-1H-indole-2-carboxamideHCID 178418339Butyllithium

Product 1

HCID 674821881-(5-chloro-1H-indol-2-yl)pentan-1-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a cooled (−78° C.) solution of the title compound of Example 1 Step A (2.40 g, 10.1 mmol) in THF (30 mL) was added n-BuLi (15.7 mL, 1.6 M in hexanes, 25.1 mmol), and the mixture was stirred for 1.5 h, whereupon it was transferred to a 0° C. bath. After 45 min, the reaction mixture was quenched by addition of 2 N aq. HCl. The aqueous phase was extracted with EtOAc, and the organic phase was dried over anhydrous Na2SO4 and concentrated in vacuo. Purification by flash chromatography on silica gel (0 to 25%, then 25 to 100% EtOAc in hexanes) provided the title compound: LCMS A, tr=3.74 min, m/z 236.1 [M+H]+; 1H NMR (500 MHz, CDCl3) □9.34 (br s, 1H), 7.68 (d, J=2.0 Hz, 1H), 7.37 (d, J=8.5 Hz, 1H), 7.29 (dd, J=8.5, 1.5 Hz, 1H), 7.13 (d, J=1.5 Hz, 1 H), 2.95 (t, J=7.5 Hz, 2H), 1.80-1.74 (m, 2H), 1.47-1.40 (m, 2H), 0.97 (t, J=7.5 Hz, 3H).

Workup

  1. customwas transferred to a 0° C.
  2. waitAfter 45 min
  3. customthe reaction mixture was quenched by addition of 2 N aq. HCl
  4. extractionThe aqueous phase was extracted with EtOAc
  5. dry with materialthe organic phase was dried over anhydrous Na2SO4
  6. concentrationconcentrated in vacuo
  7. customPurification by flash chromatography on silica gel (0 to 25%

Sources & evidence

ORD record
ord-adacf08b9bba4df1bdd2a503995ee0c3
Source dataset
uspto-grants-2009_10
Patent number
US07598398B2

Reaction notes

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