Allyl bromide → HCID 178457167, compound

HRID 1007528Notes

Reaction equation

HRID 1007528 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][NH:11][C@H:12]2[CH2:17][CH2:16][C@H:15]([C:18]3[CH:27]=[CH:26][C:21]4[NH:22][C:23](=[O:25])[O:24][C:20]=4[CH:19]=3)[CH2:14][CH2:13]2)=[CH:4][CH:3]=1.C([O-])(O)=O.[Na+].[CH2:33](Br)[CH:34]=[CH2:35]>C1COCC1.CN(C=O)C.O>[CH2:35]([N:11]([CH2:10][CH2:9][CH2:8][C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1)[C@H:12]1[CH2:17][CH2:16][C@H:15]([C:18]2[CH:27]=[CH:26][C:21]3[NH:22][C:23](=[O:25])[O:24][C:20]=3[CH:19]=2)[CH2:14][CH2:13]1)[CH:34]=[CH2:33]

Participants

7

Reactant 3

HCID 7841Allyl bromide2×HCID 516892Sodium Bicarbonate2×HCID 178518612HCID 178518612, compound

Product 1

HCID 178457167HCID 178457167, compoundYield 34.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred suspension of 6-{trans-4-[3-(4-fluorophenyl)-propylamino]-cyclohexyl}-3H-benzoxazol-2-one (400 mg, 0.99 mmol) in THF (40 mL) and DMF (3 mL) was added NaHCO3 (180 mg, 2.2 mmol) and allyl bromide (130 mg, 1.1 mmol). After refluxing overnight, additional DMF (1.5 mL), allyl bromide (30 mg, 29 mmoL), and NaHCO3 (21 mg, 0.25 mmol) were added. The reaction mixture was refluxed for 12 hours and then cooled to room temperature. The material was diluted with water and extracted with EtOAc (3×). The combined organics were washed with water, saturated NaCl solution (3×), dried (Na2SO4), filtered, and concentrated under reduced pressure. Purification by flash chromatography (silica, 90:10 CH2Cl2:MeOH), followed by formation of the HCl salt, gave 6-(trans-4-{allyl-[3-(4-fluorophenyl)propyl]-amino}cyclohexyl)-3H-benzoxazol-2-one (138 mg, 31%), as a white solid: mp 224-230° C.; IR (KBr): 2943, 1770, 1510 cm−1; 1H NMR (500 MHz, DMSO-d6): δ 11.51 (s, 1H), 10.38 (br s, 1H), 7.31-7.28 (m, 2H), 7.17-7.11 (m, 3H), 7.00 (s, 2H), 6.11-6.04 (m, 1H), 5.55 (d, J=17 Hz, 1H), 5.45 (d, J=10 Hz, 1H), 3.87-3.71 (m, 2H), 3.38-3.31 (m, 1H), 3.19-3.13 (m, 1H), 3.05-2.92 (m, 1H), 2.70-2.51 (m, 3H), 2.18-2.12 (m, 2H), 2.07-1.99 (m, 2H), 1.92-1.87 (m, 2H), 1.72-1.50 (m, 4H); (ESI-MS (m/z): 409 [M+H]+; HPLC: method B, 11.34 minutes (98.1%); Anal. Calcd for C25H29FN2O2.HCl: C, 67.48; H, 6.80; N, 6.30. Found: C, 67.29; H, 6.93; N, 6.07.

Workup

  1. temperatureAfter refluxing overnight
  2. temperatureThe reaction mixture was refluxed for 12 hours
  3. extractionextracted with EtOAc (3×)
  4. washThe combined organics were washed with water, saturated NaCl solution (3×)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification by flash chromatography (silica, 90:10 CH2Cl2:MeOH)

Sources & evidence

ORD record
ord-dce95335de4248239dc60e180e8ea89d
Source dataset
uspto-grants-2004_09
Patent number
US06794402B2

Reaction notes

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