Potassium Carbonate → 2-(4-Bromo-2-fluorophenyl)-2-(4-ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)acetamide

HRID 1525922Notes

Reaction equation

HRID 1525922 reaction equation
Br[CH:2]([C:6]1[CH:11]=[CH:10][C:9]([Br:12])=[CH:8][C:7]=1[F:13])[C:3]([NH2:5])=[O:4].Cl.[CH2:15]([N:17]1[CH2:22][C:21]2([CH2:27][CH2:26][NH:25][CH2:24][CH2:23]2)[O:20][CH2:19][C:18]1=[O:28])[CH3:16].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.[Cl-].[Na+].O>[Br:12][C:9]1[CH:10]=[CH:11][C:6]([CH:2]([N:25]2[CH2:26][CH2:27][C:21]3([O:20][CH2:19][C:18](=[O:28])[N:17]([CH2:15][CH3:16])[CH2:22]3)[CH2:23][CH2:24]2)[C:3]([NH2:5])=[O:4])=[C:7]([F:13])[CH:8]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 712710764-Ethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one hydrochlorideHCID 867254262-Bromo-2-(4-bromo-2-fluorophenyl)acetamide

Product 1

HCID 712709392-(4-Bromo-2-fluorophenyl)-2-(4-ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)acetamideYield 62.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a mixture of 2-bromo-2-(4-bromo-2-fluorophenyl)acetamide (250 mg, 0.8 mmol) and 4-ethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one hydrochloride (189 mg, 0.8 mmol) in N,N-dimethylformamide (2 mL) at 23° C. was added potassium carbonate (333 mg, 2.4 mmol). The reaction mixture was stirred for 3 h and then was poured into brine (100 mL) and extracted with ether (3×100 mL). The combined organic layers were washed with brine (3×50 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. Purification of the residue by flash chromatography (0-100% ethyl acetate/hexanes) afforded the title product (214 mg, 62%). MS(ES)+ m/e 428 [M+H]+; 1H NMR (400 MHz, CD3CN) δ ppm 1.07 (t, J=7.07 Hz, 3 H) 1.65-1.77 (m, 2 H) 1.79-1.91 (m, 2 H) 2.10-2.16 (m, 1 H) 2.44 (br. s., 1 H) 2.54 (s, 1 H) 2.66 (br. s., 1 H) 3.17 (s, 2 H) 3.35 (q, J=7.16 Hz, 2 H) 3.93 (d, J=1.52 Hz, 2 H) 4.39 (s, 1 H) 6.00 (br. s., 1 H) 7.19 (br. s., 1 H) 7.27-7.35 (m, 1 H) 7.39 (t, J=2.27 Hz, 1 H) 7.41 (t, J=2.15 Hz, 1 H).

Workup

  1. extractionextracted with ether (3×100 mL)
  2. washThe combined organic layers were washed with brine (3×50 mL)
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification of the residue by flash chromatography (0-100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-25f4dd56c0694647bfe557a1982899e3
Source dataset
uspto-grants-2015_07
Patent number
US09084794B2

Reaction notes

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