Methyl iodide → 2-{4-[(1R,2S)-2-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)cyclopropyl]piperidin-1-yl}-5-(methoxymethyl)pyridine

HRID 1474736Notes

Reaction equation

HRID 1474736 reaction equation
[Si:1]([O:8][CH2:9][CH2:10][C@@H:11]1[CH2:13][C@@H:12]1[CH:14]1[CH2:19][CH2:18][N:17]([C:20]2[N:25]=[CH:24][C:23]([CH2:26][OH:27])=[CH:22][CH:21]=2)[CH2:16][CH2:15]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH3:28][Si]([N-][Si](C)(C)C)(C)C.[Na+].CI>C1COCC1>[Si:1]([O:8][CH2:9][CH2:10][C@@H:11]1[CH2:13][C@@H:12]1[CH:14]1[CH2:19][CH2:18][N:17]([C:20]2[CH:21]=[CH:22][C:23]([CH2:26][O:27][CH3:28])=[CH:24][N:25]=2)[CH2:16][CH2:15]1)([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 89584039(6-{4-[(1R,2S)-2-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)cyclopropyl]piperidin-1-yl}pyridin-3-yl)methanol

Product 1

HCID 1232968832-{4-[(1R,2S)-2-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)cyclopropyl]piperidin-1-yl}-5-(methoxymethyl)pyridine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of the (6-{4-[(1R,2S)-2-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)cyclopropyl]piperidin-1-yl}pyridin-3-yl)methanol (0.3 g, 0.768 mmol) in THF (1.920 ml) was cooled at ice-bath temperature. A solution of NaHMDS (0.922 ml, 0.922 mmol) was added followed by addition of methyl iodide (0.067 ml, 1.075 mmol). The bath was removed and the resulting mixture stirred at room temperature for 2 hours. The mixture was diluted with 1N NaOH (50 ml), extracted with EtOAc (3×30 ml), the organic fractions combined, washed with brine, dried over sodium sulfate, filtered and the volatiles removed in vacuo. The residue was purified by column chromatography on silica gel, Biotage 25 g, using a gradient eluant of 0-30% EtOAc/hexanes to afford the title compound. LC/MS (m/z): 405 (M+H)+.

Workup

  1. customThe bath was removed
  2. additionThe mixture was diluted with 1N NaOH (50 ml)
  3. extractionextracted with EtOAc (3×30 ml)
  4. washwashed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customthe volatiles removed in vacuo
  8. customThe residue was purified by column chromatography on silica gel, Biotage 25 g

Sources & evidence

ORD record
ord-843004e3f80e4b12bb9f5b10208a108d
Source dataset
uspto-grants-2015_04
Patent number
US09018224B2

Reaction notes

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