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

HRID 1396867ノート

反応式

HRID 1396867 の反応式
[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

参加物

7

反応物 5

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

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]+).

後処理

  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)

出典と根拠

ORDレコード
ord-f6aa37e15d644bd398c37bafaa32fae1
出典データセット
uspto-grants-2014_12
特許番号
US08901119B2

反応ノート

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