Acetic Acid → 1-{(2R)-2-(cyclopentylmethyl)-4-[(1,1-dimethylethyl)oxy]-4-oxobutanoyl}-4,5-dihydro-1H-pyrazole-5-carboxylic acid

HRID 1396867노트

반응식

HRID 1396867 반응식
[NH:1]1[CH:5]([C:6]([OH:8])=[O:7])[CH2:4][CH:3]=[N:2]1.CCN(C(C)C)C(C)C.[CH:18]1([CH2:23][C@@H:24]([C:33](F)=[O:34])[CH2:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][CH2:21][CH2:20][CH2:19]1.C(O)(=O)C.[Cl-].[NH4+]>ClCCl>[CH:18]1([CH2:23][C@H:24]([CH2:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[C:33]([N:1]2[CH:5]([C:6]([OH:8])=[O:7])[CH2:4][CH:3]=[N:2]2)=[O:34])[CH2:19][CH2:20][CH2:21][CH2:22]1

참가 물질

7

반응물 5

HCID 176Acetic AcidHCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 128798564,5-dihydro-1H-pyrazole-5-carboxylic acidHCID 86706344HCID 86706344, 화합물

생성물 1

HCID 682877191-{(2R)-2-(cyclopentylmethyl)-4-[(1,1-dimethylethyl)oxy]-4-oxobutanoyl}-4,5-dihydro-1H-pyrazole-5-carboxylic acid수율 57.4%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

To a solution of 4,5-dihydro-1H-pyrazole-5-carboxylic acid (1.44 g, 8.8 mmol) in dichloromethane (DCM) (62 ml) at 0° C. was added Hunig's base (9.25 ml, 53.0 mmol) followed by 1,1-dimethylethyl (3R)-3-(cyclopentylmethyl)-4-fluoro-4-oxobutanoate (3.8 g, 8.8 mmol) in 10 mL DCM. The resulting mixture was allowed to warm to room temperature and stirred for 4 hours. The mixture was then cooled to 0° C. and acetic acid (2.5 ml, 44.1 mmol) was added, followed by sat. aq ammonium chloride (15 mL). The phases were separated and the aqueous phase was extracted once with DCM (20 mL). The combined organics were washed with brine (15 mL), dried over sodium sulfate, and concentrated to yield a yellow oil. This crude product was purified by Combiflash automated silica gel chromatography (0-100% EtOAc in hex) to afford 1-{(2R)-2-(cyclopentylmethyl)-4-[(1,1-dimethylethyl)oxy]-4-oxobutanoyl}-4,5-dihydro-1H-pyrazole-5-carboxylic acid (1.78 g, 5.05 mmol, 57% yield) as a clear oil. MS: 353 ([M+H]+).

후처리

  1. temperatureThe mixture was then cooled to 0° C.
  2. customThe phases were separated
  3. extractionthe aqueous phase was extracted once with DCM (20 mL)
  4. washThe combined organics were washed with brine (15 mL)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customto yield a yellow oil
  8. customThis crude product was purified by Combiflash automated silica gel chromatography (0-100% EtOAc in hex)

출처 및 근거

ORD 기록
ord-f6aa37e15d644bd398c37bafaa32fae1
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08901119B2

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