Ethyl 4-bromobutyrate → 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 1514231Notes

Reaction equation

HRID 1514231 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].Br[CH2:30][CH2:31][CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34].CCN(C(C)C)C(C)C>C(#N)C.CCOC(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]([CH2:30][CH2:31][CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])[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

6

Reactant 3

HCID 76300Ethyl 4-bromobutyrate2×HCID 81531Diisopropylethylamine2×HCID 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]butanoateYield 63.7%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 22728543Water ethylacetateSolvent

Procedure

A solution 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) (179 mg, 0.424 mmol), ethyl 4-bromobutanoate (0.061 ml, 0.424 mmol) and DIPEA (0.074 ml, 0.424 mmol) in Acetonitrile (5 ml) was heated at 70° C. overnight. Additional ethyl 4-bromobutanoate (0.061 ml, 0.424 mmol) and DIPEA (0.074 ml, 0.424 mmol) were added and the reaction heated for a further 5 hrs. The cooled reaction was diluted with EtOAc/water, separated, the organics dried over magnesium sulphate and evaporated. Purified by flash chromatography eluting with EtOAc/iso-hexane 1:2 to give the title compound (135 mg) as a colourless oil. MS (ES): C26H3035ClN3O5 requires 499; found 500 [M+H]+.

Workup

  1. temperaturethe reaction heated for a further 5 hrs
  2. customThe cooled reaction
  3. customseparated
  4. dry with materialthe organics dried over magnesium sulphate
  5. customevaporated
  6. customPurified by flash chromatography
  7. washeluting with EtOAc/iso-hexane 1:2

Sources & evidence

ORD record
ord-98dae194fbd54d6c99eaac17fac695de
Source dataset
uspto-grants-2012_07
Patent number
US08222245B2

Reaction notes

Loading…