Ammonia → ((S)-1-carbamoylbut-3-ynyl)carbamic acid tert-butyl ester

HRID 2112425Notes

Reaction equation

HRID 2112425 reaction equation
Cl.C[N:3](C)CCCN=C=NCC.[C:13]([O:17][C:18]([NH:20][CH:21]([CH2:25][C:26]#[CH:27])[C:22](O)=[O:23])=[O:19])([CH3:16])([CH3:15])[CH3:14].ON1C2C=CC=CC=2N=N1.N>CN(C)C=O.C(OCC)(=O)C>[C:13]([O:17][C:18](=[O:19])[NH:20][C@H:21]([C:22](=[O:23])[NH2:3])[CH2:25][C:26]#[CH:27])([CH3:16])([CH3:15])[CH3:14]

Participants

7

Reactant 4

HCID 222AmmoniaHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 35131712-((Tert-butoxycarbonyl)amino)pent-4-ynoic acid

Product 1

HCID 45092143((S)-1-carbamoylbut-3-ynyl)carbamic acid tert-butyl esterYield 22.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

At 0° C., 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (563 mg, 2.94 mmol) was added to a solution of commercially available (S)-2-(tert-butyoxycarbonylaminopent-4-ynoic acid (e.g. Acros, 626 mg, 2.94 mmol) and 1-hydroxybenzotriazole (397 mg, 2.94 mmol) in N,N-dimethylformamide (20 ml). The reaction mixture was stirred at 0° C. for 20 min. A 25% aqueous solution of ammonia (2.38 ml) was added. The reaction mixture was stirred for 16 h, while warming up to room temperature. It was diluted with ethyl acetate (150 ml) and washed with a 10% aqueous solution of sodium hydrogensulphate (150 ml). The aqueous phase was extracted with ethyl acetate (2×100 ml). The combined organic layers were washed with brine (250 ml) and dried over magnesium sulphate. The solvent was removed in vacuo. The residue was dissolved in ethyl acetate (100 ml) and washed with a mixture of brine (75 ml) and water (75 ml). The aqueous phase was extracted with ethyl acetate (2×50 ml). The combined organic layers were dried over magnesium sulphate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (50 g), using dichloromethane/methanol (10:1) as eluent, to give 138 mg of ((S)-1-carbamoylbut-3-ynyl)carbamic acid tert-butyl ester.

Workup

  1. stirringThe reaction mixture was stirred for 16 h
  2. temperaturewhile warming up to room temperature
  3. washwashed with a 10% aqueous solution of sodium hydrogensulphate (150 ml)
  4. extractionThe aqueous phase was extracted with ethyl acetate (2×100 ml)
  5. washThe combined organic layers were washed with brine (250 ml)
  6. dry with materialdried over magnesium sulphate
  7. customThe solvent was removed in vacuo
  8. dissolutionThe residue was dissolved in ethyl acetate (100 ml)
  9. washwashed with a mixture of brine (75 ml) and water (75 ml)
  10. extractionThe aqueous phase was extracted with ethyl acetate (2×50 ml)
  11. dry with materialThe combined organic layers were dried over magnesium sulphate
  12. customThe solvent was removed in vacuo
  13. customThe crude product was purified by flash chromatography on silica (50 g)

Sources & evidence

ORD record
ord-d81411a173f04dac8f460c57f4f003b5
Source dataset
uspto-grants-2009_04
Patent number
US07524813B2

Reaction notes

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