1-Chloro-3-iodobenzene → HCID 11625627, compound

HRID 1992058Notes

Reaction equation

HRID 1992058 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4](I)[CH:3]=1.[Mg].[C:10]([C:12](=[C:18]1[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]1)[C:13]([O:15][CH2:16][CH3:17])=[O:14])#[N:11]>C(OCC)C.O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C:18]2([CH:12]([C:10]#[N:11])[C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:19][CH2:20][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:22][CH2:23]2)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 122691-Chloro-3-iodobenzeneHCID 5462224MagnesiumHCID 11551073TERT-BUTYL 4-(1-CYANO-2-ETHOXY-2-OXOETHYLIDENE)PIPERIDINE-1-CARBOXYLATE

Product 1

HCID 11625627HCID 11625627, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 1-chloro-3-iodobenzene (14.1 g, 59.28 mmol) in diethyl ether (12 ml) was added dropwise to a mixture of magnesium turnings (1.59 g, 65.4 mmol) in diethyl ether (50 ml) at room temperature. When the Grignard reaction was complete, the resulting organomagnesium reagent was added dropwise to a stirred mixture of compound 16a (5.0 g, 17 mmol) and cuprous iodide (800 mg, 4.2 mmol) in tetrahydrofuran (30 mL) cooled to 0° C. The reaction mixture was stirred 1 hour at 0° C. and then quenched with saturated ammonium chloride solution. Ethyl acetate (500 ml) was added and the mixture was washed successively with saturated ammonium chloride, water and brine. The organic layer was dried and concentrated and the resulting crude material was purified by column chromatography on silica gel eluting with 4:1 hexane:ethyl acetate. This afforded tert-butyl 4-(3-chlorophenyl)-4-(1-cyano-2-ethoxy-2-oxoethyl)piperidine-1-carboxylate (16b) as an oil (5.2 g, 75%). 1H NMR (400 MHz, CDCl3): δ 7.37-7.26 (m, 4H), 3.99 (br.q, 2H, J=6 Hz), 3.91 (br m, 2H), 3.58 (s, 1H), 2.88 (br.m, 2H), 2.52 (ddd, 2H, J=6, 4, 3 Hz), 2.04 (m, 2H), 1.43 (s, 9H), and 1.06 (t, 3H, J=6 Hz). ES-LCMS m/z 429 (M+Na+).

Workup

  1. customWhen the Grignard reaction
  2. customquenched with saturated ammonium chloride solution
  3. additionEthyl acetate (500 ml) was added
  4. washthe mixture was washed successively with saturated ammonium chloride, water and brine
  5. customThe organic layer was dried
  6. concentrationconcentrated
  7. customthe resulting crude material was purified by column chromatography on silica gel eluting with 4:1 hexane

Sources & evidence

ORD record
ord-a9db1065d16b4a3a96385251f5845082
Source dataset
uspto-grants-2010_01
Patent number
US07645771B2

Reaction notes

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