Benzyl Bromide → HCID 86755450, compound

HRID 1420862Notes

Reaction equation

HRID 1420862 reaction equation
[ClH:1].[CH3:2][O:3][C:4]1[CH:9]=[CH:8][C:7]([O:10][C:11]([F:14])([F:13])[F:12])=[CH:6][C:5]=1[C@H:15]1[CH2:19][C@@:18]2([CH2:24][CH2:23][CH2:22][NH:21][C@H:20]2[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[O:17][CH2:16]1.C(=O)([O-])[O-].[K+].[K+].[CH2:37](Br)[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>CN(C)C=O.O>[ClH:1].[CH2:37]([N:21]1[CH2:22][CH2:23][CH2:24][C@:18]2([O:17][CH2:16][C@@H:15]([C:5]3[CH:6]=[C:7]([O:10][C:11]([F:14])([F:12])[F:13])[CH:8]=[CH:9][C:4]=3[O:3][CH3:2])[CH2:19]2)[C@@H:20]1[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1)[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1

Participants

6

Reactant 3

HCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 21969046HCID 21969046, compound

Product 1

HCID 86755450HCID 86755450, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

(3R,5R,6S)-3-(2-Methoxy-5-(trifluoromethoxy)phenyl)-6-phenyl-1-oxa-7-aza-spiro[4,5]decane hydrochloride (Example 165, 100 mg, 0.2 mmol) and potassium carbonate (38 mg) were dissolved in dimethyl formamide (0.5 mL). Benzyl bromide (0.3 mL) was added and the mixture was stirred at room temperature overnight, then at 60° C. for 3 h. The mixture was cooled, diluted with water (10 mL) and extracted into ether (3×10 mL). The combined organic fractions were washed with brine, dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was dissolved in ethyl acetate (5 mL) and ethereal hydrogen chloride (1 M, 1 mL) was added. The solid was collected and dried in vacuo to give the title compound as a crystalline solid (19 mg). 1H NMR (360 MHz, d6 -DMSO) δ 1.75 (3H, m), 2.01 (2H, m), 2.22 (2H, m), 2.96 (1H, m) 3.63 (3H, s), 3.67 (1H, m), 3.92 (1H, m), 4.01 (1H, m), 4.41 (1H, d, J 9.74 Hz), 6.92 (1H, d, J 8.9 Hz), 7.05 (1H, s), 7.13 (1H, d, J 8.65 Hz), 7.31 (2H, d, J 6.53 Hz), 7.42 (3H, m), 7.60 (4H, m), and 7.91 (1H, m).

Workup

  1. waitat 60° C. for 3 h
  2. temperatureThe mixture was cooled
  3. extractionextracted into ether (3×10 mL)
  4. washThe combined organic fractions were washed with brine
  5. dry with materialdried (MgSO4)
  6. customthe solvent was evaporated under reduced pressure
  7. dissolutionThe residue was dissolved in ethyl acetate (5 mL)
  8. additionethereal hydrogen chloride (1 M, 1 mL) was added
  9. customThe solid was collected
  10. customdried in vacuo

Sources & evidence

ORD record
ord-7ef2f203fbd643ec8ed188287a0920ff
Source dataset
uspto-grants-2000_06
Patent number
US06071927

Reaction notes

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