Lithium diisopropylamide → HCID 69253567, compound

HRID 902756Notes

Reaction equation

HRID 902756 reaction equation
[CH3:1][O:2][C:3](=[O:42])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH2:12][CH2:13][CH2:14][N:15]([CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([C:37]([F:40])([F:39])[F:38])[C:32]=2[Cl:41])[CH2:16][CH:17]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:6]=1.[CH:43]([N-]C(C)C)([CH3:45])[CH3:44].[Li+].IC(I)(C)C>C1COCC1>[CH3:1][O:2][C:3]([C:4]1([C:5]2[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH2:12][CH2:13][CH2:14][N:15]([CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([C:37]([F:38])([F:39])[F:40])[C:32]=3[Cl:41])[CH2:16][CH:17]([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)[C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH:6]=2)[CH2:45][CH2:43][CH2:44]1)=[O:42]

Participants

5

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 10188816Methyl (3-{3-[[2-Chloro-3-(trifluoromethyl)benzyl](2,2-diphenylethyl)amino]propoxy}-phenyl)acetateHCID 11483316Propane, 2,2-diiodo-

Product 1

HCID 69253567HCID 69253567, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of (3-{3-[(2-Chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-acetic acid methyl ester (100 mg, 0.17 mmol) in dry THF (50 ml) was added lithium diisopropylamide (1.26 ml, 0.5 mmol) dropwise with cooling to −78° C. After the reaction mixture was stirred at −78° C. for an additional 1 h, diiodo-propane (152 mg, 0.51 mmol) was added. The reaction was warmed to room temperature over 4 h followed by quenching with saturated ammonium chloride (10 ml). Solvent was removed and the residue was partitioned between water and ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate and concentrated under vacuum. The residue was purified by silica gel column chromatograph (EtOAc:Hexane/20:80) to give the title compound as an oil (40 mg, 50%). MS m/e 636.2 (M+H)+.

Workup

  1. temperatureThe reaction was warmed to room temperature over 4 h
  2. customby quenching with saturated ammonium chloride (10 ml)
  3. customSolvent was removed
  4. customthe residue was partitioned between water and ethyl acetate
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under vacuum
  8. customThe residue was purified by silica gel column chromatograph (EtOAc:Hexane/20:80)

Sources & evidence

ORD record
ord-188c931b03f745a5b9f1532c22186a9d
Source dataset
uspto-grants-2008_04
Patent number
US07365085B2

Reaction notes

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