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Tetrabutylammonium Fluoride → 2-[(1S,2R)-2-{1-[5-(methoxymethyl)pyridin-2-yl]piperidin-4-yl}cyclopropyl]ethanol

HRID 1474737
Notes
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Reaction equation

HRID 1474737 reaction equation
[Si]([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(C)(C)C)(C)C.[CH3:28]CCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.[OH-].[Na+]>[CH3:28][O:27][CH2:26][C:23]1[CH:22]=[CH:21][C:20]([N:17]2[CH2:16][CH2:15][CH:14]([C@H:12]3[CH2:13][C@H:11]3[CH2:10][CH2:9][OH:8])[CH2:19][CH2:18]2)=[N:25][CH:24]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 89584039(6-{4-[(1R,2S)-2-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)cyclopropyl]piperidin-1-yl}pyridin-3-yl)methanol

Product 1

HCID 895841062-[(1S,2R)-2-{1-[5-(methoxymethyl)pyridin-2-yl]piperidin-4-yl}cyclopropyl]ethanol

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent
HCID 14798
Sodium Hydroxide
Solvent

Procedure

The (6-{4-[(1R,2S)-2-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)cyclopropyl]piperidin-1-yl}pyridin-3-yl)methanol (2.471 ml, 0.494 mmol) was dissolved in THF (1.236 ml) and TBAF (0.741 ml, 0.741 mmol) added. The mixture was stirred at room temperature for 1 hour. 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 0-100% EtOAc/hexanes to afford the title compound. LC/MS (m/z): 291 (M+H)+.

Workup

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

Sources & evidence

ORD record
ord-ddc48764503c4f98bc72851c1e05b6d5
Source dataset
uspto-grants-2015_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09018224B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes