Hexachloroethane → HCID 71285111, compound

HRID 1481758Notes

Reaction equation

HRID 1481758 reaction equation
[CH2:1]([O:8][C:9]1[N:18]=[C:17]([C:19]2[CH:20]=[C:21]3[C:25](=[CH:26][CH:27]=2)[N:24]([CH3:28])[CH:23]=[C:22]3[C:29]#[N:30])[C:16]([CH2:31][CH3:32])=[C:15]([O:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[C:10]=1[C:11]([O:13][CH3:14])=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li+].CC([N-]C(C)C)C.[Cl:49]C(Cl)(Cl)C(Cl)(Cl)Cl>C1COCC1>[CH2:1]([O:8][C:9]1[N:18]=[C:17]([C:19]2[CH:20]=[C:21]3[C:25](=[CH:26][CH:27]=2)[N:24]([CH3:28])[C:23]([Cl:49])=[C:22]3[C:29]#[N:30])[C:16]([CH2:31][CH3:32])=[C:15]([O:33][CH2:34][C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)[C:10]=1[C:11]([O:13][CH3:14])=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 6214HexachloroethaneHCID 2724682Lithium diisopropylamideHCID 71284559HCID 71284559, compound

Product 1

HCID 71285111HCID 71285111, compoundYield 82.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of methyl 2,4-bis(benzyloxy)-6-(3-cyano-1-methyl-1H-indol-5-yl)-5-ethylnicotinate (1.80 g, 3.39 mmol), prepared in Example 359 step 2, in THF (24 mL) was added LDA solution (1.5M in cyclohexane, 3.40 mL, 5.10 mmol, 1.5 eq) dropwise at −78° C. The reaction mixture was stirred for 15 min before a solution of hexachloroethane (1.21 g, 5.1 mmol, 1.5 eq) in THF (6 mL) was added dropwise at −78° C. The reaction progress was monitored by LC-MS. Upon completion, the reaction was quenched with sat. NH4Cl solution then extracted with Et2O (4×30 mL). The combined organic layers were dried over Na2SO4 then concentrated to give a crude product which was purified by flash column chromatography (0-10% EtOAc in 1/1 CH2Cl2/hexanes) to afford the title compound (1.58 g, 82%).

Workup

  1. additionwas added dropwise at −78° C
  2. customUpon completion, the reaction was quenched with sat. NH4Cl solution
  3. extractionthen extracted with Et2O (4×30 mL)
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. concentrationthen concentrated
  6. customto give a crude product which
  7. customwas purified by flash column chromatography (0-10% EtOAc in 1/1 CH2Cl2/hexanes)

Sources & evidence

ORD record
ord-ad5fca4480294cb1a594b8b4b2d06091
Source dataset
uspto-grants-2016_08
Patent number
US09409905B2

Reaction notes

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