Water → Tert-butyl (s)-1-((s)-1-((2s,4s)-4-amino-2-((r)-1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-ylamino)-1-oxopropan-2-yl(methyl)carbamate

HRID 237243Notes

Reaction equation

HRID 237243 reaction equation
[N:1]([C@@H:4]1[CH2:8][N:7]([C:9](=[O:29])[C@@H:10]([NH:15][C:16](=[O:28])[C@@H:17]([N:19]([CH3:27])[C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[CH3:18])[C:11]([CH3:14])([CH3:13])[CH3:12])[C@H:6]([C:30](=[O:42])[NH:31][C@H:32]2[C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[CH2:35][CH2:34][CH2:33]2)[CH2:5]1)=[N+]=[N-].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.O.COC(C)(C)C>C1COCC1>[NH2:1][C@@H:4]1[CH2:8][N:7]([C:9](=[O:29])[C@@H:10]([NH:15][C:16](=[O:28])[C@@H:17]([N:19]([CH3:27])[C:20](=[O:26])[O:21][C:22]([CH3:23])([CH3:24])[CH3:25])[CH3:18])[C:11]([CH3:13])([CH3:14])[CH3:12])[C@H:6]([C:30](=[O:42])[NH:31][C@H:32]2[C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[CH2:35][CH2:34][CH2:33]2)[CH2:5]1

Participants

6

Reactant 4

HCID 962WaterHCID 11776TriphenylphosphineHCID 23212559water MeOtBuHCID 57661012Tert-butyl (s)-1-((s)-1-((2s,4s)-4-azido-2-((r)-1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-ylamino)-1-oxopropan-2-yl(methyl)carbamate

Product 1

HCID 57806830Tert-butyl (s)-1-((s)-1-((2s,4s)-4-amino-2-((r)-1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-ylamino)-1-oxopropan-2-yl(methyl)carbamate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of the title compound of Example 3 (1.7 g, 2.9 mmol) in 10.6 mL dry THF was added Ph3P (765 mg, 2.9 mmol) at room temperature. Water (78.3 μL, 4.35 mmol) was added drop wise and the reaction mixture was allowed to stir for 16 hours at room temperature. A 1:1 mixture of water/MeOtBu was added to quench the reaction. The two phases were separated. The aqueous phase was extracted by EtOAc twice, and then the combined organic phase was washed by brine, dried over sodium sulfate and concentrated under reduced pressure. The residue was chromatographed on silica gel, eluting with EtOAc, the 5% to 15% MeOH/methylene chloride to give the title compound as a white foam-like solid. 1H NMR (CDCl3): consistent with proposed structure.

Workup

  1. additionwas added
  2. customto quench
  3. customthe reaction
  4. customThe two phases were separated
  5. extractionThe aqueous phase was extracted by EtOAc twice
  6. washthe combined organic phase was washed by brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was chromatographed on silica gel
  10. washeluting with EtOAc

Sources & evidence

ORD record
ord-dc74f16d97bd48b3879596316d6a897e
Source dataset
uspto-grants-2014_02
Patent number
US08642554B2

Reaction notes

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