2-Bromoethanol → 3-(Fluoromethyl)-1-azetidineethanol

HRID 717501Notes

Reaction equation

HRID 717501 reaction equation
F[C:2](F)(F)[C:3]([OH:5])=O.[F:8][CH2:9][CH:10]1[CH2:13][NH:12][CH2:11]1.BrCCO.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[F:8][CH2:9][CH:10]1[CH2:13][N:12]([CH2:2][CH2:3][OH:5])[CH2:11]1

Participants

5

Reactant 3

HCID 108982-BromoethanolHCID 11430Potassium CarbonateHCID 896201983-(fluoromethyl)azetidine, trifluoroacetic acid2×

Product 1

HCID 896196853-(Fluoromethyl)-1-azetidineethanolYield 78.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 3-(fluoromethyl)azetidine 2,2,2-trifluoroacetate (Intermediate 6, 100 mg, 0.5 mmol), 2-bromoethanol (60 mg, 0.5 mmol), and potassium carbonate (0.2 g, 1.5 mmol) in acetonitrile (5 mL) was heated to 80° C. overnight. After cooling, solids were filtered off and washed with acetonitrile. The filtrate was concentrated on a rotary evaporator to give a residue that was purified by silica gel chromatography eluting with 10:7 ethyl acetate/hexanes to 10:7:2:1 ethyl acetate/hexane/methanol/triethylamine to afford 52 mg of 2-(3-(fluoromethyl)azetidin-1-yl)ethanol as a pale yellow oil. 1H NMR (DMSO-d6): δ 5.13 (t, 1H), 4.62 (d, 1H), 4.50 (d, 1H), 4.06 (t, 2H), 3.84 (dd, 2H), 3.54 (q, 2H), 3.11 (t, 2H), 3.06-3.03 (m, 1H).

Workup

  1. temperatureAfter cooling
  2. filtrationsolids were filtered off
  3. washwashed with acetonitrile
  4. concentrationThe filtrate was concentrated on a rotary evaporator
  5. customto give a residue that
  6. customwas purified by silica gel chromatography
  7. washeluting with 10:7 ethyl acetate/hexanes to 10:7:2:1 ethyl acetate/hexane/methanol/triethylamine

Sources & evidence

ORD record
ord-7dfecb60b6ff483daf8c1cb994cf660a
Source dataset
uspto-grants-2015_11
Patent number
US09193714B2

Reaction notes

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