tert-Butanol → HCID 66970921, compound

HRID 1361524Notes

Reaction equation

HRID 1361524 reaction equation
Cl.[C@@H:2]12[CH2:8][C@@H:5]([CH2:6][CH2:7]1)[CH2:4][C@H:3]2[N:9]1[CH2:14][CH2:13][CH:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[O:21][CH3:22])[CH2:11][CH2:10]1.[C:23](O)([CH3:26])([CH3:25])[CH3:24].[Cl-].[Cl-].[Cl-].[Al+3]>[N+](C1C=CC=CC=1)([O-])=O>[C@@H:2]12[CH2:8][C@@H:5]([CH2:6][CH2:7]1)[CH2:4][C@H:3]2[N:9]1[CH2:10][CH2:11][CH:12]([C:15]2[CH:20]=[C:19]([C:23]([CH3:26])([CH3:25])[CH3:24])[CH:18]=[CH:17][C:16]=2[O:21][CH3:22])[CH2:13][CH2:14]1

Participants

5

Reactant 3

HCID 6386tert-ButanolHCID 6451240Aluminum(III) ChlorideHCID 66971120HCID 66971120, compound

Product 1

HCID 66970921HCID 66970921, compound

Reagents, catalysts & solvents 1

HCID 7416NitrobenzeneSolvent2×

Procedure

1-((1S,2R,4R)-bicyclo[2.2.1]heptan-2-yl)-4-(2-methoxyphenyl)piperidine hydrochloride (397, 64 mg, 0.20 mmol) was suspended in nitrobenzene (1.0 mL) and treated with 1.0 eq tert-butanol (15 mg), followed by 3.0 eq of aluminum trichloride in nitrobenzene (600 μL 1.0 M solution, 0.60 mmol). The reaction was stirred at room temperature for 2 hours, then quenched with 1.0 N HCl (5.0 mL). The aqueous layer was separated, basified with 1.0 N NaOH (pH 12) and extracted with dichloromethane (10 mL). The extract was dried (Na2SO4), filtered, concentrated in vacuo and dissolved in methanol:acetonitrile (1.0 mL, 1:1 v/v). The solution was filtered (Whatman 0.2 μm PTFE) and subjected to reverse-phase HPLC purification (5-50% CH3CN/0.08% TFA) to yield [1-((1S,2R,4R)-bicyclo[2.2.1]heptan-2-yl)-4-(5-tert-butyl-2-methoxy-phenyl)piperidine] (compound no. 325) as the TFA salt. LC/MS (RP-C18, 10-99% CH3CN/0.05% TFA gradient over 5 min) m/z 342.2 [M+H]+, retention time 2.70 min.

Workup

  1. customquenched with 1.0 N HCl (5.0 mL)
  2. customThe aqueous layer was separated
  3. extractionextracted with dichloromethane (10 mL)
  4. dry with materialThe extract was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. dissolutiondissolved in methanol
  8. filtrationThe solution was filtered (Whatman 0.2 μm PTFE)
  9. customsubjected to reverse-phase HPLC purification (5-50% CH3CN/0.08% TFA)

Sources & evidence

ORD record
ord-ff61da1a6ae7423aae9c4e2d9f478731
Source dataset
uspto-grants-2011_02
Patent number
US07880007B2

Reaction notes

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