Methyl iodide → Exo-8-boc-8-azabicyclo[3.2.1]octane-3-carboxylic acid methyl ester

HRID 537122Notes

Reaction equation

HRID 537122 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@H:13]2[CH2:14][CH2:15][C@@H:9]1[CH2:10][CH:11]([C:16]([OH:18])=[O:17])[CH2:12]2)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:19](=O)([O-])[O-].[K+].[K+].CI>CN(C)C=O.C(OCC)(=O)C>[C@@H:13]12[N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[C@@H:9]([CH2:15][CH2:14]1)[CH2:10][CH:11]([C:16]([O:18][CH3:19])=[O:17])[CH2:12]2

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 50999080exo-8-Boc-8-azabicyclo(3.2.1)octane-3-carboxylic acid

Product 1

HCID 67491395Exo-8-boc-8-azabicyclo[3.2.1]octane-3-carboxylic acid methyl esterYield 92.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (1R,5S)-8-(tert-butoxycarbonyl)-8-azabicyclo[3.2.1]octane-3-carboxylic acid (500 mg, 1.96 mmol) in N,N-dimethylformamide (5 mL) was added potassium carbonate (541 mg, 3.92 mmol) and methyl iodide (0.18 mL, 2.94 mmol). The reaction was stirred at room temperature for 18 hours. The reaction was diluted with ethyl acetate (50 mL) and heptanes (50 mL), and then washed with water (100 mL) and brine (50 mL). The organics were dried over sodium sulfate, filtered, and concentrated. Purification by flash column chromatography gave the title compound (486 mg, 92%) as a clear oil. 1H NMR (400 MHz, CDCl3, δ): 4.17-4.29 (m, 2H), 3.65 (s, 3H), 2.75-2.86 (m, 1H), 1.93-2.01 (m, 2H), 1.79-1.92 (m, 2H), 1.67-1.76 (m, 2H), 1.58-1.66 (m, 2H), 1.45 (s, 9H).

Workup

  1. washwashed with water (100 mL) and brine (50 mL)
  2. dry with materialThe organics were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-bcc69acaeca941248ed62ba0c8ef6e86
Source dataset
uspto-grants-2014_10
Patent number
US08859773B2

Reaction notes

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