Pyridine, hydrofluoride (1:1) → Benzyl 4-fluoro-4-(hydroxymethyl)piperidine-1-carboxylate

HRID 47309Notes

Reaction equation

HRID 47309 reaction equation
N1C=CC=CC=1.[FH:7].[O:8]1[C:10]2([CH2:15][CH2:14][N:13]([C:16]([O:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[O:17])[CH2:12][CH2:11]2)[CH2:9]1.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[F:7][C:10]1([CH2:9][OH:8])[CH2:15][CH2:14][N:13]([C:16]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:17])[CH2:12][CH2:11]1

Participants

5

Reactant 3

HCID 64774Pyridine, hydrofluoride (1:1)HCID 516892Sodium BicarbonateHCID 13016598Benzyl 1-oxa-6-azaspiro(2.5)octane-6-carboxylate

Product 1

HCID 22135584Benzyl 4-fluoro-4-(hydroxymethyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 5 ml hydrogen fluoride pyridine and 20 ml methylene chloride was cooled, and 10 ml solution of 4.95 g of benzyl 1-oxa-6-azaspiro[2.5]octane-6-carboxylate in methylene chloride was added dropwise thereinto over 25 min such that the bulk temperature was 0° C. or less. The mixture was stirred for 35 min under ice-cooling. The reaction solution was poured into a mixture of saturated sodium bicarbonate and ice. The organic layer was recovered, dried over anhydrous magnesium sulfate, and filtered. The filtrate was evaporated, and then subjected to silica gel column chromatography to give 2.84 g of the title compound.

Workup

  1. temperaturewas cooled
  2. temperaturecooling
  3. customThe organic layer was recovered
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. customThe filtrate was evaporated

Sources & evidence

ORD record
ord-6485205fb097437fba4475970ed3c25a
Source dataset
uspto-grants-2004_03
Patent number
US06699870B2

Reaction notes

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