Bromoacetyl bromide → tert-Butyl 4-[2-bromo-N-[4-(trifluoromethyl)phenyl]acetamido]piperidine-1-carboxylate

HRID 1667207Notes

Reaction equation

HRID 1667207 reaction equation
[F:1][C:2]([F:24])([F:23])[C:3]1[CH:8]=[CH:7][C:6]([NH:9][CH:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]2)=[CH:5][CH:4]=1.C(N(C(C)C)C(C)C)C.[Br:34][CH2:35][C:36](Br)=[O:37]>O1CCCC1.C(OCC)(=O)C>[Br:34][CH2:35][C:36]([N:9]([CH:10]1[CH2:11][CH2:12][N:13]([C:16]([O:18][C:19]([CH3:21])([CH3:20])[CH3:22])=[O:17])[CH2:14][CH2:15]1)[C:6]1[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:23])[F:24])=[CH:8][CH:7]=1)=[O:37]

Participants

6

Reactant 3

HCID 61147Bromoacetyl bromideHCID 81531DiisopropylethylamineHCID 220291421-Boc-4-(4-Trifluoromethyl-phenylamino)-piperidine

Product 1

HCID 67445908tert-Butyl 4-[2-bromo-N-[4-(trifluoromethyl)phenyl]acetamido]piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A solution of the product of Example 166A (480 mg, 1.39 mmol) and N-ethyl-N-isopropylpropan-2-amine (0.486 mL, 2.79 mmol) in anhydrous tetrahydrofuran (10 mL) was cooled in an ice water bath for 10 minutes followed by the dropwise addition of bromoacetyl bromide (0.146 mL, 1.67 mmol) via syringe. The reaction was stirred for 30 minutes at 0° C., then 1 hour at ambient temperature and 3 hours at reflux. The reaction mixture was cooled to ambient temperature and diluted with ethyl acetate. The organic solution was washed with 1 N aqueous HCl and saturated NaHCO3 solution and brine, dried with Na2SO4, filtered, and concentrated in vacuo. The crude product was chromatographed on silica gel (Analogix® Intelliflash™ 280; SF25-60 g column; 50% ethyl acetate/hexanes) which yielded the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 7.74 (d, J=8.4, 2H), 7.34 (d, J=8.2, 2H), 4.80-4.66 (m, 1H), 4.25-4.04 (m, 2H), 3.49 (s, 2H), 2.79 (t, J=12.4, 2H), 1.87-1.77 (m, 2H), 1.39 (s, 9H), 1.29-1.11 (m, 2H); MS (DCI+) m/z 482/484 (M+NH4)+.

Workup

  1. temperature1 hour at ambient temperature and 3 hours at reflux
  2. temperatureThe reaction mixture was cooled to ambient temperature
  3. washThe organic solution was washed with 1 N aqueous HCl and saturated NaHCO3 solution and brine
  4. dry with materialdried with Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was chromatographed on silica gel (Analogix® Intelliflash™ 280; SF25-60 g column; 50% ethyl acetate/hexanes) which

Sources & evidence

ORD record
ord-1aa1cb090210495e9c03da96d3356b9e
Source dataset
uspto-grants-2011_10
Patent number
US08044069B2

Reaction notes

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