Ammonia → 2-Trimethylsilanylethyl 4-((s)-1-tert-butoxycarbonylamino-1-methoxycarbonyl-but-3-enyl)piperidine-1-carboxylate

HRID 1743262Notes

Reaction equation

HRID 1743262 reaction equation
N.[Na].[CH2:3]([C@:6]1([CH:32]2[CH2:37][CH2:36][N:35]([C:38]([O:40][CH2:41][CH2:42][Si:43]([CH3:46])([CH3:45])[CH3:44])=[O:39])[CH2:34][CH2:33]2)[C:11](=[O:12])[O:10][C@@H:9](C2C=CC=CC=2)[C@@H](C2C=CC=CC=2)[N:7]1[C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH:4]=[CH2:5].[Cl-].[NH4+].C[Si](C=[N+]=[N-])(C)C>C1COCC1.CO.CCCCCC.C(O)(=O)C.C(O)C>[C:28]([O:27][C:25]([NH:7][C@@:6]([CH:32]1[CH2:37][CH2:36][N:35]([C:38]([O:40][CH2:41][CH2:42][Si:43]([CH3:46])([CH3:45])[CH3:44])=[O:39])[CH2:34][CH2:33]1)([C:11]([O:10][CH3:9])=[O:12])[CH2:3][CH:4]=[CH2:5])=[O:26])([CH3:29])([CH3:30])[CH3:31]

Participants

11

Reactant 5

HCID 222Ammonia2×HCID 25517Ammonium ChlorideHCID 167693TrimethylsilyldiazomethaneHCID 5360545SodiumHCID 90954080Tert-butyl (3s,5r,6s)-3-allyl-2-oxo-5,6-diphenyl-3-[1-(2-trimethylsilanylethoxycarbonyl)piperidin-4-yl]morpholine-4-carboxylate

Product 1

HCID 696515972-Trimethylsilanylethyl 4-((s)-1-tert-butoxycarbonylamino-1-methoxycarbonyl-but-3-enyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 5

HCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
0 °C

Procedure

50 ml of ammonia were condensed at −78° C. 340 mg of sodium were added in 2 portions at an interval of 10 min in each case and the mixture was stirred for 20 min. At −60° C., a solution of 916 mg of tert-butyl (3S,5R,6S)-3-allyl-2-oxo-5,6-diphenyl-3-[1-(2-trimethylsilanylethoxycarbonyl)piperidin-4-yl]morpholine-4-carboxylate and 866 μl of ethanol in 50 ml of THF was added dropwise. The mixture was stirred at −45° C. for 1.5 h, and the reaction was stopped by adding solid ammonium chloride until the blue color disappeared. The ammonia was then allowed to evaporate off, and 150 ml of water were added to the residue. The THF was removed in vacuo. The aqueous was adjusted to pH 2 with 1 N HCl and extracted 3 times with 100 ml of ethyl acetate each time. The combined organic phases were dried with MgSO4. The solvents were removed in vacuo, and the residue was filtered through silica gel with 4% methanol in dichloromethane. The product obtained in this way was taken up in 5 ml of methanol and cooled to 0° C. 0.5 ml of a 2 N solution of trimethylsilyldiazomethane in hexane was added thereto 5 times at intervals of 1.5 hours each. 2 ml of acetic acid were then added dropwise, and the mixture was stirred at room temperature for 1 h. The solvents were removed in vacuo and the residue was chromatographed on silica gel.

Workup

  1. customcondensed at −78° C
  2. stirringThe mixture was stirred at −45° C. for 1.5 h
  3. customto evaporate off
  4. addition150 ml of water were added to the residue
  5. customThe THF was removed in vacuo
  6. extractionextracted 3 times with 100 ml of ethyl acetate each time
  7. dry with materialThe combined organic phases were dried with MgSO4
  8. customThe solvents were removed in vacuo
  9. filtrationthe residue was filtered through silica gel with 4% methanol in dichloromethane
  10. customThe product obtained in this way
  11. customat intervals of 1.5 hours
  12. stirringthe mixture was stirred at room temperature for 1 h
  13. customThe solvents were removed in vacuo
  14. customthe residue was chromatographed on silica gel

Sources & evidence

ORD record
ord-58e5eb2983b245cca925f02d1f121d3d
Source dataset
uspto-grants-2006_03
Patent number
US07008957B2

Reaction notes

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