Hydrochloric Acid → (1S,4S)-methyl 4-(tert-butoxycarbonylamino)-1-(2-(tert-butyldimethylsilyloxy)ethyl)cyclopent-2-enecarboxylate

HRID 1747142ノート

反応式

HRID 1747142 の反応式
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[C:11]([O:15][C:16]([NH:18][C@H:19]1[CH2:23][C@@H:22]([C:24]([O:26][CH3:27])=[O:25])[CH:21]=[CH:20]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].[CH3:28][C:29]([Si:32]([O:35][CH2:36][CH2:37]I)([CH3:34])[CH3:33])([CH3:31])[CH3:30].Cl>C1COCC1>[C:11]([O:15][C:16]([NH:18][C@H:19]1[CH2:23][C@@:22]([CH2:37][CH2:36][O:35][Si:32]([C:29]([CH3:31])([CH3:30])[CH3:28])([CH3:34])[CH3:33])([C:24]([O:26][CH3:27])=[O:25])[CH:21]=[CH:20]1)=[O:17])([CH3:14])([CH3:13])[CH3:12]

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 2733832Lithium HexamethyldisilazideHCID 10610130(1R,4S)-methyl 4-(tert-butoxycarbonylamino)cyclopent-2-enecarboxylateHCID 11129873tert-Butyl(2-iodoethoxy)dimethylsilane

生成物 1

HCID 86708127(1S,4S)-methyl 4-(tert-butoxycarbonylamino)-1-(2-(tert-butyldimethylsilyloxy)ethyl)cyclopent-2-enecarboxylate

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒3 回

反応条件

温度
-68 °C

実験手順

To a −70° C. solution of LiHMDS in THF (1M, 6.97 L, 6.97 mol) was added a solution of the product of Step B (763.5 g, 3.16 mol) in THF (800 mL) over a 2 h period while keeping the temperature at or below −68° C. The resulting solution was stirred for 45 min at −68° C. A solution of the product of Step C (1.267 kg, 4.426 mol) in THF (800 mL) was added over 1 h 50 min period while maintaining a temperature of ˜−66° C. The reaction was stirred at ˜-66° C. for 45 min. The reaction was warmed to −15° C. and worked up by addition to mixture of aqueous HCl and ice. The mixture was extracted with toluene, the organic layer was washed with water, brine and dried over MgSO4. The organic layer was concentrated and purified on silica gel using a mixture of EtOAc in heptanes to provide the product of Step D as a clear oil. 1H NMR (400 MHz, CHLOROFORM-d) d=5.69-5.86 (m, 2H), 4.79-4.93 (m, 1H), 4.68-4.80 (m, 1H), 3.67 (s, 3H), 3.53-3.62 (m, 2H), 2.16-2.30 (m, 1H), 2.04-2.16 (m, 2H), 1.70-1.81 (m, 1H), 1.41 (s, 9H), 0.78-0.91 (m, 13H), 0.00 (s, 6H).

後処理

  1. custombelow −68° C
  2. temperaturewhile maintaining a temperature of ˜−66° C
  3. stirringThe reaction was stirred at ˜-66° C. for 45 min
  4. temperatureThe reaction was warmed to −15° C.
  5. extractionThe mixture was extracted with toluene
  6. washthe organic layer was washed with water, brine
  7. dry with materialdried over MgSO4
  8. concentrationThe organic layer was concentrated
  9. custompurified on silica gel using
  10. additiona mixture of EtOAc in heptanes

出典と根拠

ORDレコード
ord-ffd8eef9413c4e0f99f1683a2c9e791d
出典データセット
uspto-grants-2015_10
特許番号
US09150532B2

反応ノート

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