tert-Butyl bromoacetate → (R)-tert-butyl 4-((S)-4-benzyl-2-oxooxazolidin-3-yl)-3-(biphenyl-4-ylmethyl)-4-oxobutanoate

HRID 70869

反応式

HRID 70869 の反応式
[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:29])[CH2:15][CH2:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[CH:19][CH:18]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH2:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33]>C1COCC1>[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:29])[C@H:15]([CH2:16][C:17]1[CH:18]=[CH:19][C:20]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[CH:21][CH:22]=1)[CH2:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

参加物

4

反応物 2

HCID 79177tert-Butyl bromoacetateHCID 59607884(S)-4-benzyl-3-(3-(biphenyl-4-yl)propanoyl)oxazolidin-2-one2 回

生成物 1

HCID 59607858(R)-tert-butyl 4-((S)-4-benzyl-2-oxooxazolidin-3-yl)-3-(biphenyl-4-ylmethyl)-4-oxobutanoate収率 37%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒3 回

反応条件

温度
-74 °C

実験手順

A stirred solution of (S)-4-benzyl-3-(3-(biphenyl-4-yl)propanoyl)oxazolidin-2-one (intermediate 12: 5.01 g, 13.00 mmol) in THF (180 mL) is cooled to −73.8° C., and 1M THF solution of sodium hexamethyldisilylamide (14.30 mL, 14.30 mmol) is added during 5 minutes. After 30 minutes, a solution of tert-butyl bromoacetate (2.495 mL, 16.90 mmol) in THF (20 mL) is added dropwise during 5 minutes. The solution is stirred at −74° C. for 1 hour, and the reaction is quenched with saturated aqueous NH4Cl (100 mL), and warmed up to ambient temperature. The precipitated solid is filtered off and washed with ethyl acetate (50 mL). The organic phase is separated, washed with brine, dried over MgSO4, and concentrated under reduced pressure. The obtained residue is suspended in MeOH (70 mL) and then filtered to collect the solid (5.9 g) as a mixture of the desired product and the starting material. The mixture is purified by flash column chromatography on 120 g of silica gel (heptane/EtOAc=90:10 to 50:50) to give (R)-tert-butyl 4-((S)-4-benzyl-2-oxooxazolidin-3-yl)-3-(biphenyl-4-ylmethyl)-4-oxobutanoate (2.40 g, 37%). HPLC retention time=1.74 minutes (condition B); MS=499.4 (m+); 443.4 (m-tBu+1; 100%); 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.41 (s, 9 H) 2.42 (dd, J=16.67, 4.04 Hz, 1 H) 2.71 (ddd, J=16.55, 13.26, 9.60 Hz, 2 H) 2.87 (dd, J=16.93, 10.86 Hz, 1 H) 3.04 (dd, J=13.14, 6.32 Hz, 1 H) 3.32 (dd, J=13.39, 3.03 Hz, 1 H) 3.92 (t, J=8.34 Hz, 1 H) 4.07 (dd, J=8.97, 2.15 Hz, 1 H) 4.48-4.58 (m, 2 H) 7.20-7.30 (m, 3 H) 7.30-7.36 (m, 5 H) 7.42 (t, J=7.58 Hz, 2 H) 7.52 (d, J=8.1 Hz, 2 H) 7.56 (d, J=7.8 Hz, 2 H).

後処理

  1. customthe reaction is quenched with saturated aqueous NH4Cl (100 mL)
  2. temperaturewarmed up to ambient temperature
  3. filtrationThe precipitated solid is filtered off
  4. washwashed with ethyl acetate (50 mL)
  5. customThe organic phase is separated
  6. washwashed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated under reduced pressure
  9. filtrationfiltered
  10. customto collect the solid (5.9 g)
  11. additionas a mixture of the desired product
  12. customThe mixture is purified by flash column chromatography on 120 g of silica gel (heptane/EtOAc=90:10 to 50:50)

出典と根拠

ORDレコード
ord-fd86f3c73c4c42889f8efb9c9a196772
出典データセット
uspto-grants-2014_09
特許番号
US08822534B2

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