Methanesulfonic Acid → benzyl (S)-1-((1S,2R,4R)-2-acetamido-4-(isopropyl(methyl)amino)cyclohexyl)-2-oxopyrrolidin-3-ylcarbamate

HRID 2242329ノート

反応式

HRID 2242329 の反応式
C([O:5][C:6]([NH:8][C@@H:9]1[CH2:14][C@H:13]([N:15]([CH:17]([CH3:19])[CH3:18])[CH3:16])[CH2:12][CH2:11][C@@H:10]1[N:20]1[CH2:24][CH2:23][C@H:22]([NH:25][C:26](=[O:35])[O:27][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:21]1=[O:36])=O)(C)(C)C.[CH3:37]S(O)(=O)=O.C(OC(=O)C)(=O)C.[OH-].[Na+]>C1(C)C=CC=CC=1.CC(O)C.C(O)(=O)C.C(N(CC)CC)C>[C:6]([NH:8][C@@H:9]1[CH2:14][C@H:13]([N:15]([CH:17]([CH3:18])[CH3:19])[CH3:16])[CH2:12][CH2:11][C@@H:10]1[N:20]1[CH2:24][CH2:23][C@H:22]([NH:25][C:26](=[O:35])[O:27][CH2:28][C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:21]1=[O:36])(=[O:5])[CH3:37]

参加物

9

反応物 4

HCID 6395Methanesulfonic AcidHCID 7918Acetic AnhydrideHCID 14798Sodium HydroxideHCID 86618127benzyl {(S)-1-[(1S,2R,4R)-2-tert-butoxycarbonylamino-4-(isopropyl-methyl-amino)-cyclo-hexyl]-2-oxo-pyrrolidin-3-yl}-carbamate

生成物 1

HCID 44185160benzyl (S)-1-((1S,2R,4R)-2-acetamido-4-(isopropyl(methyl)amino)cyclohexyl)-2-oxopyrrolidin-3-ylcarbamate

試薬・触媒・溶媒 4

HCID 176Acetic Acid溶媒HCID 1140Toluene溶媒2 回HCID 3776Isopropanol溶媒HCID 8471Triethylamine溶媒

反応条件

温度
60 °C

実験手順

Example 1, Alternative Preparation, Step 5: The tert-Butyl carbamate 9 (50 g) was dissolved in Toluene (500 mL) and i-PrOH (150 mL). The resulting solution was then heated to 60° C. Methanesulfonic acid (19.6 mL) was added below 65° C. Upon reaction completion (HPLC), the mixture was cooled to RT and triethylamine (69.4 mL) added slowly below 25° C. Acetic anhydride was then added below 25° C. After 1 h acetic acid (250 mL) was added below 25° C. The toluene phase was discarded and 2-methyl-THF (500 mL) was added to the aqueous phase. The mixture was stirred vigorously and basified with NaOH (25% aqueous solution) to pH 12. The aqueous phase was discarded and the organic layer was washed with brine (250 mL). The organic layer was concentrated under reduced pressure and continuously replaced with i-PrOH. The solution was cooled and filtered to provide benzyl {(S)-1-[(1S,2R,4R)-2-acetylamino-4-(isopropyl-methyl-amino)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-carbamate 10 in i-PrOH solution which was used directly in the hydrogenation.

後処理

  1. customExample 1, Alternative Preparation, Step 5
  2. customUpon reaction completion (HPLC)
  3. temperaturethe mixture was cooled to RT
  4. washthe organic layer was washed with brine (250 mL)
  5. concentrationThe organic layer was concentrated under reduced pressure
  6. temperatureThe solution was cooled
  7. filtrationfiltered

出典と根拠

ORDレコード
ord-02984adb9dd341c1b9e446115eaa0b01
出典データセット
uspto-grants-2010_03
特許番号
US07671062B2

反応ノート

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