Triethylamine → tert-Butyl 4-fluoro-4-(hydroxymethyl)piperidine-1-carboxylate

HRID 1755045Notes

Reaction equation

HRID 1755045 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].C(N(CC)CC)C.[FH:23].F.F.C(N(CC)CC)C>>[C:1]([O:5][C:6]([N:8]1[CH2:15][CH2:14][C:11]([F:23])([CH2:12][OH:13])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 3

HCID 8471TriethylamineHCID 175505N,N-Diethylethanamine trihydrofluorideHCID 22135564tert-Butyl 1-oxa-6-azaspiro(2.5)octane-6-carboxylate

Product 1

HCID 22248400tert-Butyl 4-fluoro-4-(hydroxymethyl)piperidine-1-carboxylateYield 16%

Conditions

Temperature
120 °C

Procedure

1-Oxa-6-aza-spiro[2.5]octane-6-carboxylic acid tert-butyl ester (144 mg, 679 μmol), triethylamine (1.10 mL, 6.79 mmol) and triethylamine trihydrofluoride (2.85 mL, 20.4 mmol) were mixed in a sealed test tube. This mixture was stirred at 120° C. for 6.5 hours. The reaction mixture was cooled, and then quenched with a 2 N aqueous NaOH solution and extracted with ethyl acetate three times. The organic layers were combined, washed with saturated brine, dried over sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane-AcOEt) to give 4-fluoro-4-hydroxymethyl-piperidine-1-carboxylic acid tert-butyl ester (24.9 mg, 16%).

Workup

  1. temperatureThe reaction mixture was cooled
  2. customquenched with a 2 N aqueous NaOH solution
  3. extractionextracted with ethyl acetate three times
  4. washwashed with saturated brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified by silica gel column chromatography (hexane-AcOEt)

Sources & evidence

ORD record
ord-d26de71e29c3435eb25aac5e9cb48765
Source dataset
uspto-grants-2015_10
Patent number
US09169254B2

Reaction notes

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