Tetrahydrofuran → ethyl(R)-2-tert-butoxycarbonylamino-5-oxo-5-(3,4,5-trifluorophenyl)pentanoate

HRID 16334

反応式

HRID 16334 の反応式
[F:1][C:2]1[CH:3]=[C:4]([Mg]Br)[CH:5]=[C:6]([F:9])[C:7]=1[F:8].O1CCCC1.[CH3:17][CH2:18][O:19][C:20]([C@H:22]1[CH2:26][CH2:25][C:24](=[O:27])[N:23]1[C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])=[O:21].[Cl-].[NH4+]>C(OCC)(=O)C>[CH2:18]([O:19][C:20](=[O:21])[C@H:22]([NH:23][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:26][CH2:25][C:24](=[O:27])[C:4]1[CH:3]=[C:2]([F:1])[C:7]([F:8])=[C:6]([F:9])[CH:5]=1)[CH3:17]

参加物

6

反応物 4

HCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 8208851-Boc-D-Pyroglutamic acid ethyl esterHCID 178505944HCID 178505944、化合物

生成物 1

HCID 67372607ethyl(R)-2-tert-butoxycarbonylamino-5-oxo-5-(3,4,5-trifluorophenyl)pentanoate

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

反応条件

温度
-40 °C

実験手順

3,4,5-Trifluorophenyl magnesium bromide (0.35 M diethylether solution, 55 mL) was dropwise added to a tetrahydrofuran solution (100 mL) of (R)-5-oxo-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-ethyl ester (CAS Register No. 128811-48-3, 4.1 g) over 20 min at −40° C. This reaction solution was stirred at −40° C. for 5 hr. To this solution, a saturated ammonium chloride aqueous solution and ethyl acetate were added. The reaction solution was heated to room temperature. The organic layer was separated, washed with saturated saline, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (heptane ethyl acetate=1:0 to 1:1) to give 4.8 g of (R)-2-tert-butoxycarbonylamino-5-oxo-5-(3,4,5-trifluorophenyl)pentanoic acid ethyl ester. A 4 N hydrochloric acid ethyl acetate solution (30 mL) was added to an ethyl acetate solution (30 mL) of the obtained (R)-2-tert-butoxycarbonylamino-5-oxo-5-(3,4,5-trifluorophenyl)pentanoic acid ethyl ester. This solution was stirred for 16 hr. The reaction solution was concentrated under reduced pressure. To the residue, ethyl acetate and a saturated sodium hydrogencarbonate aqueous solution were added. The organic layer was separated, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. To an ethyl acetate solution (50 mL) of the residue, 10% palladium-carbon (100 mg) was added. The resulting reaction solution was stirred under 1 atm of hydrogen atmosphere for 6 hr. The reaction solution was filtered through Celite. The filtrate was concentrated under reduced pressure to give 2.91 g of the title compound. The physical property values of this compound were as follows:

後処理

  1. temperatureThe reaction solution was heated to room temperature
  2. customThe organic layer was separated
  3. washwashed with saturated saline
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (heptane ethyl acetate=1:0 to 1:1)

出典と根拠

ORDレコード
ord-49977d1cf78442ccb8202ae5dc25bd5f
出典データセット
uspto-grants-2010_06
特許番号
US07737141B2

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