Triethylamine → tert-butyl N-(4-diazo-3-oxobutan-2-yl)carbamate

HRID 519091Notes

Reaction equation

HRID 519091 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]([CH3:13])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(CC)CC.C(Cl)(=O)OCC.[N+:27](=[CH2:29])=[N-:28]>C1COCC1.CCOCC>[C:1]([O:5][C:6](=[O:7])[NH:8][CH:9]([CH3:13])[C:10](=[O:12])[CH:29]=[N+:27]=[N-:28])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 9550DiazomethaneHCID 10928Ethyl chloroformateHCID 2684712-N-Boc-aminopropionic acid

Product 1

HCID 56979712tert-butyl N-(4-diazo-3-oxobutan-2-yl)carbamateYield 99%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a −15° C. solution of 2-((tert-butoxycarbonyl)amino)propanoic acid (2.5 g, 13.21 mmol) in THF (66 mL) was added Et3N (1.337 g, 13.21 mmol) and ethyl carbonochloridate (1.434 g, 13.21 mmol). The reaction mixture was stirred for 15 min then allowed to warm to 0° C. A solution of diazomethane (prepared according to the standard procedure (Organic Syntheses, Coll. Vol. 5, p. 351 (1973); Vol. 41, p. 16 (1961)) in Et2O (150 mL) was added, until the rich yellow color persisted. The reaction mixture was allowed to warm to rt and stirred for 3 h. Excess CH2N2 was destroyed by the addition of a small amount of aqueous AcOH (20%, 3 mL). The reaction mixture was extracted with saturated NaHCO3 (20 mL), and the organic portion was separated and washed with saturated aqueous NH4Cl (20 mL) and brine (20 mL). The organic portion was separated, dried over Na2SO4, filtered and evaporated in vacuo. The residue was purified by column chromatography on silica gel (eluting with 5-20% EtOAc in petroleum ether) to give (3-diazo-1-methyl-2-oxo-propyl)-carbamic acid tert-butyl ester (2.8 g, 99%) as a brown solid. 1H NMR (DMSO-d6, 400 MHz): δ 7.27 (d, J=7.2, 1H), 6.02 (s, 1H), 4.01 (m, 1H), 1.39 (s, 9H), 1.20 (m, 3H).

Workup

  1. additionwas added, until the rich yellow color
  2. temperatureto warm to rt
  3. stirringstirred for 3 h
  4. customExcess CH2N2 was destroyed by the addition of a small amount of aqueous AcOH (20%, 3 mL)
  5. extractionThe reaction mixture was extracted with saturated NaHCO3 (20 mL)
  6. customthe organic portion was separated
  7. washwashed with saturated aqueous NH4Cl (20 mL) and brine (20 mL)
  8. customThe organic portion was separated
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. customevaporated in vacuo
  12. customThe residue was purified by column chromatography on silica gel (eluting with 5-20% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-1b7cafa19c7949d8bee5bb907e3b5d4a
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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