Triethylamine → [1-(1-Cyano-cyclopropylcarbamoyl)-cyclopropyl]-carbamic acid tert-butyl ester

HRID 2038765Notes

Reaction equation

HRID 2038765 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1([C:12]([OH:14])=O)[CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=[N:30][C:25]2[CH:26]=[CH:27]C=[N:29][C:24]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.NC1(C#N)CC1.C(N(CC)CC)C>C1COCC1>[C:1]([O:5][C:6](=[O:7])[NH:8][C:9]1([C:12](=[O:14])[NH:30][C:25]2([C:24]#[N:29])[CH2:27][CH2:26]2)[CH2:10][CH2:11]1)([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 6883961-((tert-Butoxycarbonyl)amino)cyclopropanecarboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 145863631-Amino-1-cyclopropanecarbonitrile hydrochloride

Product 1

HCID 68379019[1-(1-Cyano-cyclopropylcarbamoyl)-cyclopropyl]-carbamic acid tert-butyl esterYield 80.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of the 1-[(tert-butoxycarbonyl)amino]cyclopropanecarboxylic acid (1.7 g, 8.43 mmol), HATU (3.5 g, 9.3 mmol), and 1-aminocyclopropanecarbonitrile hydrochloride (1.0 g, 8.43 mmol) in THF (34 mL) was added triethylamine (3.5 mL, 25.3 mmol). The yellow suspension was stirred at room temperature for 18 h then most of the THF was removed in-vacuo. The remaining slurry was diluted with 150 mL 10% (w/w) aqueous Na2CO3 and 150 mL EtOAc. The layers were separated and the organic phase was washed with 10% (w/w) aqueous Na2CO3 (2×100 mL). The organic phase was washed with brine (1×75 mL), dried with Na2SO4, filtered, and concentrated to afford a crude light orange solid. This solid was triturated with Et2O and the white solid was filtered off using Et2O to rinse to yield 1.8 g of [1-(1-cyano-cyclopropylcarbamoyl)-cyclopropyl]-carbamic acid tert-butyl ester as an off-white solid, m/z 266.5 [M+H]+.

Workup

  1. custommost of the THF was removed in-vacuo
  2. additionThe remaining slurry was diluted with 150 mL 10% (w/w) aqueous Na2CO3 and 150 mL EtOAc
  3. customThe layers were separated
  4. washthe organic phase was washed with 10% (w/w) aqueous Na2CO3 (2×100 mL)
  5. washThe organic phase was washed with brine (1×75 mL)
  6. dry with materialdried with Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto afford a crude light orange solid
  10. customThis solid was triturated with Et2O
  11. filtrationthe white solid was filtered off
  12. washto rinse

Sources & evidence

ORD record
ord-f21a4ec7d3444913b07fff372fa3b9bd
Source dataset
uspto-grants-2013_11
Patent number
US08575360B2

Reaction notes

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