Boron trifluoride etherate → tert-Butyl 4-fluoro-4-(hydroxymethyl)piperidine-1-carboxylate

HRID 2112547Notes

Reaction equation

HRID 2112547 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:15][CH2:14][C:11]2([O:13][CH2:12]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].B(F)(F)[F:17].CCOCC>[OH-].[Na+]>[C:1]([O:5][C:6]([N:8]1[CH2:15][CH2:14][C:11]([F:17])([CH2:12][OH:13])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 8000Boron trifluoride etherateHCID 22135564tert-Butyl 1-oxa-6-azaspiro(2.5)octane-6-carboxylate

Product 1

HCID 22248400tert-Butyl 4-fluoro-4-(hydroxymethyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 14798Sodium HydroxideSolvent

Procedure

A mixed solution of 6-aza-1-oxaspiro[2.5]octane-6-carboxylic acid tert-butyl ester (10.0 g, 46.9 mmol) in benzene-ether (2:1) (750 mL) was cooled to 0° C., and after adding BF3.OEt2 (29.6 mL, 234 mmol) to the solution, it was stirred 1 hour. The reaction mixture was poured into ice-cooled 1N NaOH (500 ml) and stirred. After extraction with AcOEt (500 ml×3 times), the extract was washed with water and then with saturated brine, and finally dried over anhydrous MgSO4. The solvent was distilled off, and the crude product was purified by silica gel column chromatography (30% AcOEt/hexane) to obtain 4-fluoro-4-(hydroxymethyl)piperidinecarboxylic acid tert-butyl ester. The compound was identified by 1H-NMR. The yield was 4.26 g (39%).

Workup

  1. additionThe reaction mixture was poured into ice-
  2. stirringstirred
  3. extractionAfter extraction with AcOEt (500 ml×3 times)
  4. washthe extract was washed with water
  5. dry with materialwith saturated brine, and finally dried over anhydrous MgSO4
  6. distillationThe solvent was distilled off
  7. customthe crude product was purified by silica gel column chromatography (30% AcOEt/hexane)

Sources & evidence

ORD record
ord-801085c218c74131bbbf194497af396d
Source dataset
uspto-grants-2009_04
Patent number
US07524841B2

Reaction notes

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