Water → (2S,3S,5S)-5-amino-2-(N-((5-isoxazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hydroxyhexane

HRID 433778ノート

反応式

HRID 433778 の反応式
[NH2:1][C@H:2]([C@@H:10]([OH:21])[CH2:11][C@@H:12]([NH2:20])[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C1(OB(O)O)C=CC=CC=1.O.C1C([N+]([O-])=O)=CC=C([O:42][C:43]([O:45][CH2:46][C:47]2[O:51][N:50]=[CH:49][CH:48]=2)=O)C=1>C1(C)C=CC=CC=1.C1COCC1>[NH2:20][C@@H:12]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH2:11][C@H:10]([OH:21])[C@@H:2]([NH:1][C:43]([O:45][CH2:46][C:47]1[O:51][N:50]=[CH:49][CH:48]=1)=[O:42])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

参加物

7

反応物 4

HCID 962WaterHCID 78412Phenyl dihydrogen orthoborateHCID 10085299(2S,3S,5S)-2,5-Diamino-1,6-diphenylhexan-3-OLHCID 18939817((5-Isoxazolyl)methyl)-(4-nitrophenyl)carbonate

生成物 1

HCID 57164722(2S,3S,5S)-5-amino-2-(N-((5-isoxazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hydroxyhexane

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-40 °C

実験手順

A mixture of 1.54 g (5.41 mmol) of (2S,3S,5S)-2,5-diamino-1,6-diphenyl-3-hydroxyhexane and 0.673 g (5.41 mmol) of phenylboric acid in anhydrous toluene (130 mL) was heated at reflux under argon for 2 hrs with removal of H2O by a Dean-Stark trap. The resulting yellow solution was allowed to cool and the solvent was removed in vacuo to give an oil which solidified upon standing. The residue was taken up in 90 ml of THF, cooled to −40° C., and treated dropwise under Ar atmosphere over a period of 1 h with 1.11 g (3.78 mmol) of ((5-isoxazolyl)methyl)-(4-nitrophenyl)carbonate in 40 ml of THF. The solution was allowed to warm to −20° C. over the next 0.5 hr, then was stirred at 0° C. for 2.5 hrs and at room temperature for 1 hr. After removal of the solvent in vacuo, the residue was taken up in ethyl acetate (200 mL), washed sequentially with 5% aqueous K2CO3 (4×25 mL) and saturated brine (25 mL), dried over Na2SO4 and concentrated in vacuo. Silica gel chromatography of the residue using a gradient of methanol in chloroform (2%, 4%, 6%) afforded a mixture of the desired product and its regioisomer. Purification of the mixture on two consecutive 250 g SiO2 columns (deactivated with 1% isopropylamine/CH2Cl2) with a gradient of isopropylamine/CH2Cl2 (0.5%, 1%) afforded the desired compound as a sticky solid (0.730 g, 1.78 mmol, 33%): 1H NMR (DMSO-d6) δ 1.17-1.57 (m, 5H), 2.56-2.69 (m, 2H), 2.75-2.86 (m, 1H), 2.89-3.00 (m, 2H), 3.53-3.71 (m, 3H), 5.06 (s, 2H), 6.32 (d, J=2.4 Hz,1H), 7.11-7.30 (m, 10H), 8.54 (d, J=2.4 Hz, 1H). Mass spectrum: (M+H)+=410.

後処理

  1. temperaturewas heated
  2. temperatureto cool
  3. customthe solvent was removed in vacuo
  4. customto give an oil which
  5. temperatureto warm to −20° C. over the next 0.5 hr
  6. customAfter removal of the solvent in vacuo
  7. washwashed sequentially with 5% aqueous K2CO3 (4×25 mL) and saturated brine (25 mL)
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated in vacuo
  10. customafforded

出典と根拠

ORDレコード
ord-38e439a08c2743ab9425308d5c9e4fcd
出典データセット
uspto-grants-2003_12
特許番号
US06667404B2

反応ノート

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