Ethyl 4-bromobutyrate → HCID 59403518, compound

HRID 1514214Notes

Reaction equation

HRID 1514214 reaction equation
Cl.[CH3:2][CH:3]([O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:27]=[CH:26][C:20]4[CH2:21][CH2:22][NH:23][CH2:24][CH2:25][C:19]=4[CH:18]=3)[N:13]=2)=[CH:8][C:7]=1[C:28]([F:31])([F:30])[F:29])[CH3:4].CCN(C(C)C)C(C)C.Br[CH2:42][CH2:43][CH2:44][C:45]([O:47][CH2:48][CH3:49])=[O:46]>CN(C=O)C>[CH3:4][CH:3]([O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:27]=[CH:26][C:20]4[CH2:21][CH2:22][N:23]([CH2:42][CH2:43][CH2:44][C:45]([O:47][CH2:48][CH3:49])=[O:46])[CH2:24][CH2:25][C:19]=4[CH:18]=3)[N:13]=2)=[CH:8][C:7]=1[C:28]([F:30])([F:31])[F:29])[CH3:2]

Participants

5

Reactant 3

HCID 76300Ethyl 4-bromobutyrate2×HCID 81531DiisopropylethylamineHCID 68467900HCID 68467900, compound

Product 1

HCID 59403518HCID 59403518, compoundYield 87.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

7-{5-[4-[(1-Methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl}-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (Example 19) (160 mg, 0.353 mmol), DIPEA (0.234 ml, 1.342 mmol) and ethyl 4-bromobutanoate (0.110 ml, 0.767 mmol) were stirred at room temperature in DMF (10 ml) for 5 hours. The reaction mixture was then heated to 60° C. for 5 h, and allowed to stand overnight at room temperature. Further ethyl 4-bromobutanoate (0.055 ml, 0.383 mmol) was added and the reaction mixture heated at 60° C. for 6 hours. The reaction mixture was partitioned between EtOAc (˜30 ml) and water (˜30 ml) and the aqueous layer extracted once more with EtOAc (˜40 ml). The combined organics were concentrated in vacuo to yield the title compound (183 mg, 0.310 mmol) as an orange solid. MS (ES): C28H32F3N3O4 requires 531; found 532 [M+H]+.

Workup

  1. temperaturethe reaction mixture heated at 60° C. for 6 hours
  2. customThe reaction mixture was partitioned between EtOAc (˜30 ml) and water (˜30 ml)
  3. extractionthe aqueous layer extracted once more with EtOAc (˜40 ml)
  4. concentrationThe combined organics were concentrated in vacuo

Sources & evidence

ORD record
ord-3387c91dd00d4073bc05ab742cfe237e
Source dataset
uspto-grants-2012_07
Patent number
US08222245B2

Reaction notes

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