Triethylamine → Methyl (s)-1-((s)-2-(2-diazoacetyl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate

HRID 1471020Notes

Reaction equation

HRID 1471020 reaction equation
[CH3:1][O:2][C:3]([NH:5][C@@H:6]([CH:17]([CH3:19])[CH3:18])[C:7]([N:9]1[CH2:13][CH2:12][CH2:11][C@H:10]1[C:14]([OH:16])=O)=[O:8])=[O:4].CCN(CC)CC.ClC(OCC(C)C)=O.[N+:35](=[CH2:37])=[N-:36]>O1CCCC1.CCOCC>[N+:35](=[CH:37][C:14]([C@@H:10]1[CH2:11][CH2:12][CH2:13][N:9]1[C:7](=[O:8])[C@@H:6]([NH:5][C:3](=[O:4])[O:2][CH3:1])[CH:17]([CH3:19])[CH3:18])=[O:16])=[N-:36]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 9550DiazomethaneHCID 62365Isobutyl chloroformateHCID 12071044(S)-1-((S)-2-((Methoxycarbonyl)amino)-3-methylbutanoyl)pyrrolidine-2-carboxylic acid

Product 1

HCID 131731308Methyl (s)-1-((s)-2-(2-diazoacetyl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamateYield 75%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of Example 37B (100 mg, 0.367 mmol) and Et3N (154 μL, 1.102 mmol) in tetrahydrofuran (4 mL) at 0° C. was added Isobutyl chloroformate (50 μL, 0.386 mmol). Mixture was then stirred at 0° C. for 30 minutes followed by addition of excess diazomethane in Et2O. Mixture was allowed to slowly come to ambient temperature over 3 hours. Mixture was then concentrated and diluted with EtOAc. Organic was then washed with saturated aqueous NaHCO3 and brine. Organic was dried (MgSO4), filtered and concentrated. Purification by chromatography (silica gel, 100% EtOAc) afforded 82 mg (75%) of the title compound. MS (ESI) m/z 297 (M+H)+.

Workup

  1. waitto slowly come to ambient temperature over 3 hours
  2. concentrationMixture was then concentrated
  3. additiondiluted with EtOAc
  4. washOrganic was then washed with saturated aqueous NaHCO3 and brine
  5. dry with materialOrganic was dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by chromatography (silica gel, 100% EtOAc)

Sources & evidence

ORD record
ord-f6aac5a412524792840bbaa0034f2b6c
Source dataset
uspto-grants-2015_04
Patent number
US09006387B2

Reaction notes

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