Butyl ether → HCID 11573332, compound

HRID 1361525Notes

Reaction equation

HRID 1361525 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:22][CH3:23])=[C:6]([CH:8]2[CH2:13][CH2:12][N:11]([C:14]3([C:20]#N)[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]3)[CH2:10][CH2:9]2)[CH:7]=1.C[Mg]Br.C(OCCCC)CCC>O1CCCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:22][CH3:23])=[C:6]([CH:8]2[CH2:9][CH2:10][N:11]([C:14]3([CH3:20])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19]3)[CH2:12][CH2:13]2)[CH:7]=1

Participants

5

Reactant 3

HCID 8909Butyl etherHCID 70798107HCID 70798107, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 11573332HCID 11573332, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Intermediate 13a (0.5 mmol) from above was dissolved in anhydrous tetrahydrofuran (1.0 mL) and treated with 2.0 eq methylmagnesium bromide in butyl ether (1.0 mL 1.0 M solution, 1.0 mmol). The vial was flushed with nitrogen and stirred at room temperature for 3 h. The reaction was diluted with ethyl acetate (5.0 mL), quenched with saturated aqueous ammonium chloride (1.0 mL) and stirred overnight at room temperature. The organic layer was separated, concentrated in vacuo, then dissolved in methanol:acetonitrile (3.0 mL, 1:1 v/v) and subjected to reverse-phase HPLC purification (5-50% CH3CN/0.08% TFA) to yield 4-(5-chloro-2-methoxyphenyl)-1-(1-methylcyclo-hexyl)piperidine (compound no. 300) as the TFA salt. LC/MS (RP-C18, 10-99% CH3CN/0.05% TFA gradient over 5 min) m/z 322.0 [M+H]+, retention time 2.39 min.

Workup

  1. customThe vial was flushed with nitrogen
  2. additionThe reaction was diluted with ethyl acetate (5.0 mL)
  3. customquenched with saturated aqueous ammonium chloride (1.0 mL)
  4. stirringstirred overnight at room temperature
  5. customThe organic layer was separated
  6. concentrationconcentrated in vacuo
  7. dissolutiondissolved in methanol
  8. customacetonitrile (3.0 mL, 1:1 v/v) and subjected to reverse-phase HPLC purification (5-50% CH3CN/0.08% TFA)

Sources & evidence

ORD record
ord-ac826684f602492cb3d96cf78ec9f8d1
Source dataset
uspto-grants-2011_02
Patent number
US07880007B2

Reaction notes

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