Potassium Iodide → Ethyl 4-[9-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1,4-benzoxazepin-4(5H)-yl]butanoate

HRID 1514232Notes

Reaction equation

HRID 1514232 reaction equation
Cl.[Cl:2][C:3]1[CH:4]=[C:5]([C:13]2[O:17][N:16]=[C:15]([C:18]3[C:28]4[O:27][CH2:26][CH2:25][NH:24][CH2:23][C:22]=4[CH:21]=[CH:20][CH:19]=3)[N:14]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:12])[CH3:11].C(=O)([O-])[O-].[K+].[K+].[I-].[K+].Br[CH2:38][CH2:39][CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42]>CN(C)C=O.O>[Cl:2][C:3]1[CH:4]=[C:5]([C:13]2[O:17][N:16]=[C:15]([C:18]3[C:28]4[O:27][CH2:26][CH2:25][N:24]([CH2:38][CH2:39][CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH2:23][C:22]=4[CH:21]=[CH:20][CH:19]=3)[N:14]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:12])[CH3:11]

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 76300Ethyl 4-bromobutyrateHCID 684654949-(5-{3-Chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepine hydrochloride

Product 1

HCID 59403438Ethyl 4-[9-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1,4-benzoxazepin-4(5H)-yl]butanoate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 9-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepine hydrochloride (Example 31) (20 g, 47.4 mmol), potassium carbonate (16.4 g, 118 mmol) and potassium iodide (7.86 g, 47.4 mmol) in N,N-dimethylformamide (DMF) (250 ml) was treated with ethyl 4-bromobutanoate (7.46 ml, 52.1 mmol) and the resulting mixture stirred at 80° C. under nitrogen for 180 minutes. The mixture was allowed to cool and poured into water (1000 ml). The resulting precipitate was extracted into ethyl acetate (3×250 ml) and the extracts combined, washed with water (2×250 ml), then brine (150 ml), dried (sodium sulphate) and evaporated to give a colourless viscous oil. The crude material was purified by chromatography on silica, eluting with a 20-100% gradient of ethyl acetate in isohexane to give the title compound as a colourless, viscous oil which crystallised on standing (18.3 g).

Workup

  1. temperatureto cool
  2. extractionThe resulting precipitate was extracted into ethyl acetate (3×250 ml)
  3. washwashed with water (2×250 ml)
  4. dry with materialbrine (150 ml), dried (sodium sulphate)
  5. customevaporated
  6. customto give a colourless viscous oil
  7. customThe crude material was purified by chromatography on silica
  8. washeluting with a 20-100% gradient of ethyl acetate in isohexane

Sources & evidence

ORD record
ord-41df72a8e3084cf3a5f27f6aee12265c
Source dataset
uspto-grants-2012_07
Patent number
US08222245B2

Reaction notes

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