Diisopropylamine → (2R,4S)-N-allyloxycarbonyl-2-(1-tert-butyldimethylsilyl-2,4-dioxoimidazolidin-5-ylmethyl)-4-tritylthiopyrrolidine

HRID 1492820Notes

Reaction equation

HRID 1492820 reaction equation
C(NC(C)C)(C)C.[Si:8]([N:15]1[CH2:21][C:19](=[O:20])[N:18]([Si](C(C)(C)C)(C)C)[C:16]1=[O:17])([C:11]([CH3:14])([CH3:13])[CH3:12])([CH3:10])[CH3:9].CN(C)P(=O)(N(C)C)N(C)C.[CH2:40]([O:43][C:44]([N:46]1[CH2:50][C@@H:49]([S:51][C:52]([C:65]2[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=2)([C:59]2[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=2)[C:53]2[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=2)[CH2:48][C@H:47]1[CH2:71]I)=[O:45])[CH:41]=[CH2:42].[Cl-].[NH4+]>O1CCCC1.C(OCC)(=O)C>[CH2:40]([O:43][C:44]([N:46]1[CH2:50][C@@H:49]([S:51][C:52]([C:65]2[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=2)([C:59]2[CH:60]=[CH:61][CH:62]=[CH:63][CH:64]=2)[C:53]2[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=2)[CH2:48][C@H:47]1[CH2:71][CH:21]1[N:15]([Si:8]([C:11]([CH3:12])([CH3:13])[CH3:14])([CH3:9])[CH3:10])[C:16](=[O:17])[NH:18][C:19]1=[O:20])=[O:45])[CH:41]=[CH2:42]

Participants

8

Reactant 5

HCID 7912DiisopropylamineHCID 12679HexamethylphosphoramideHCID 25517Ammonium ChlorideHCID 57112975(2S,4S)-N-allyloxycarbonyl-2-iodomethyl-4-tritylthiopyrrolidineHCID 67750274N,N'-bis(tert-butyldimethylsilyl)hydantoin

Product 1

HCID 67750039(2R,4S)-N-allyloxycarbonyl-2-(1-tert-butyldimethylsilyl-2,4-dioxoimidazolidin-5-ylmethyl)-4-tritylthiopyrrolidineYield 45.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

A 1.6M n-butyllithium-hexane solution (4.1 ml, 6.56 mmol) was dropwise added to a solution of diisopropylamine (1 ml, 7.14 mmol) in tetrahydrofuran (5 ml) under a nitrogen stream at -78° C., and the reaction solution was stirred at the same temperature for 10 minutes and under cooling with ice for 30 minutes. A solution of N,N'-bis(tert-butyldimethylsilyl)hydantoin (1.65 g, 5.02 mmol) in tetrahydrofuran (2 ml) was dropwise added to this reaction solution at -78° C. This solution was stirred at the same temperature for 1 hour. Then, hexamethylphosphoric triamide (1.75 ml, 10 mmol) was added to this reaction solution, and the mixture was stirred for 10 minutes Then, a solution of (2S,4S)-N-allyloxycarbonyl-2-iodomethyl-4-tritylthiopyrrolidine (2.28 g, 4.00 mmol, compound of Reference Example 21-2) in tetrahydrofuran (3 ml) was dropwise added thereto. The reaction solution was stirred at the same temperature for 2 hours. To the reaction solution, a saturated ammonium chloride aqueous solution (10 ml) and ethyl acetate (300 ml) were added. The organic layer was washed sequentially with a 1N potassium hydrogen sulfate aqueous solution, water and a saturated sodium chloride aqueous solution and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was subjected to silica gel column chromatography (Wakogel™ C-300, hexane-ethyl acetate) to obtain (2R,4S)-N-allyloxycarbonyl-2-(1-tert-butyldimethylsilyl-2,4-dioxoimidazolidin-5-ylmethyl)-4-tritylthiopyrrolidine (1.19 g, yield: 45%).

Workup

  1. temperatureunder cooling with ice for 30 minutes
  2. stirringThis solution was stirred at the same temperature for 1 hour
  3. stirringthe mixture was stirred for 10 minutes
  4. stirringThe reaction solution was stirred at the same temperature for 2 hours
  5. washThe organic layer was washed sequentially with a 1N potassium hydrogen sulfate aqueous solution, water
  6. dry with materiala saturated sodium chloride aqueous solution and then dried over anhydrous sodium sulfate
  7. distillationThe solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-3defab9464a94df085bdee6b69d77d5f
Source dataset
uspto-grants-1994_12
Patent number
US05374720

Reaction notes

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