Ammonia → HCID 18641548, compound

HRID 346363Notes

Reaction equation

HRID 346363 reaction equation
[N:1]([CH2:4][CH:5]([OH:35])[CH2:6][S:7][CH2:8][C@@H:9]1[CH2:13][C@@H:12]([O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])[CH2:11][N:10]1[C:22]([O:24][CH2:25][C:26]1[CH:31]=[CH:30][C:29]([N+:32]([O-:34])=[O:33])=[CH:28][CH:27]=1)=[O:23])=[N+]=[N-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N.[N+:56]([C:59]1[CH:69]=[CH:68][C:62]([CH2:63][O:64][C:65](Cl)=[O:66])=[CH:61][CH:60]=1)([O-:58])=[O:57].[OH-].[Na+]>N1C=CC=CC=1.C(OCC)(=O)C.C(Cl)(Cl)Cl.O1CCCC1>[N+:56]([C:59]1[CH:60]=[CH:61][C:62]([CH2:63][O:64][C:65]([NH:1][CH2:4][CH:5]([OH:35])[CH2:6][S:7][CH2:8][C@@H:9]2[CH2:13][C@@H:12]([O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])[CH2:11][N:10]2[C:22]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][C:29]([N+:32]([O-:34])=[O:33])=[CH:28][CH:27]=2)=[O:23])=[O:66])=[CH:68][CH:69]=1)([O-:58])=[O:57]

Participants

10

Reactant 5

HCID 222AmmoniaHCID 11776TriphenylphosphineHCID 14798Sodium HydroxideHCID 782054-Nitrobenzyl chloroformateHCID 57121689HCID 57121689, compound

Product 1

HCID 18641548HCID 18641548, compoundYield 89.8%

Reagents, catalysts & solvents 4

HCID 1049PyridineSolventHCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (2S,4R)-2-[(3-azido-2-hydroxypropyl)thiomethyl]-4-t-butyldimethylsilyloxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (1.94 g) in pyridine (6 ml) was added triphenylphosphine (1.55 g) and the mixture was stirred at ambient temperature for 1 hour. To the reaction mixture was added conc. ammonia (0.50 ml) and the mixture was allowed to stand overnight at ambient temperature. The reaction mixture was concentrated under reduced pressure. The resulting mixture was dissolved in ethyl acetate (40 ml) and the solution was washed with saturated aqueous sodium chloride, dried over magnesium sulfate and evaporated in vacuo to give (2S,4R)-2-[(3-amino-2-hydroxypropyl)thiomethyl]-4-t-butyldimethylsilyloxy-1-(4-nitrobenzyloxycarbonyl)pyrroliidine. The residue containing the compound obtained above was dissolved in a mixture of ethyl acetate and water (3:1 V/V, 40 ml). To the solution was dropwise added a solution of 4-nitrobenzyloxycarbonyl chloride (0.87 g) in tetrahydrofuran (3 ml) with stirring at 2°-5° C., keeping the pH between 9-10 with 1N sodium hydroxide. The mixture was stirred at the same temperature for 1 hour. The organic layer was separated, washed with saturated aqueous sodium chloride, dried over magnesium sulfate and evaporated in vacuo. The resulting residue was chromatographed on silica gel (100 g) eluting with a mixture of dichloromethane and acetone (9:1 v/v). The fractions containing the desired compound were collected and evaporated in vacuo to give (2S,4R)-2-{3-(4-nitrobenzyloxycarbonyl)amino-2hydroxypropyl}thiomethyl-4-t-butyldimethylsilyloxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (2.25 g).

Workup

  1. waitto stand overnight at ambient temperature
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. dissolutionThe resulting mixture was dissolved in ethyl acetate (40 ml)
  4. washthe solution was washed with saturated aqueous sodium chloride
  5. dry with materialdried over magnesium sulfate
  6. customevaporated in vacuo
  7. customto give (2S,4R)-2-[(3-amino-2-hydroxypropyl)thiomethyl]-4-t-butyldimethylsilyloxy-1-(4-nitrobenzyloxycarbonyl)pyrroliidine
  8. additionThe residue containing the compound
  9. customobtained
  10. stirringwith stirring at 2°-5° C.
  11. stirringThe mixture was stirred at the same temperature for 1 hour
  12. customThe organic layer was separated
  13. washwashed with saturated aqueous sodium chloride
  14. dry with materialdried over magnesium sulfate
  15. customevaporated in vacuo
  16. customThe resulting residue was chromatographed on silica gel (100 g)
  17. washeluting with a mixture of dichloromethane and acetone (9:1 v/v)
  18. additionThe fractions containing the desired compound
  19. customwere collected
  20. customevaporated in vacuo

Sources & evidence

ORD record
ord-c787b68ed99743cdbf41c61262c8de78
Source dataset
uspto-grants-1991_10
Patent number
US05061804

Reaction notes

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