4-Methylmorpholine → tert-Butyl (1-(methoxycarbamoyl)cyclopropyl)carbamate

HRID 1503792Notes

Reaction equation

HRID 1503792 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].Cl.[O:16]([NH2:18])[CH3:17].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1>CN(C=O)C>[CH3:17][O:16][NH:18][C:12]([C:9]1([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH2:10][CH2:11]1)=[O:14]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 521874O-Methylhydroxylamine hydrochlorideHCID 6883961-((tert-Butoxycarbonyl)amino)cyclopropanecarboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 86722603tert-Butyl (1-(methoxycarbamoyl)cyclopropyl)carbamateYield 36%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1-((tert-butoxycarbonyl)amino)cyclopropanecarboxylic acid (2.00 g, 9.94 mmol), methoxylamine hydrochloride (1.09 g, 13.02 mmol), EDC.HCl (2.50 g, 13.02 mmol), HOBT (1.99 g, 13.02 mmol) and N-methylmorpholine (2.61 g, 25.8 mmol) were dissolved in anhydrous DMF (20.0 mL) and the resulting reaction mixture was stirred at RT for 5 days. The reaction mixture was evaporated to dryness and the residue was taken up in DCM and washed with saturated aqueous NaHCO3. The organic layer was dried (MgSO4), filtered and evaporated to dryness. The residue was chromatographed on a silica gel column eluting with 70% EtOAc/hexanes to afford the title compound (0.82 g, 36%): 1H NMR (400 MHz, DMSO-d6) δ 11.01 (s, 1H), 7.23 (s, 1H), 3.53 (s, 3H), 1.38 (s, 9H), 1.20 (q, J=4.3 Hz, 2H), 0.85 (q, J=4.3 Hz, 2H). This material is used without further purification.

Workup

  1. customthe resulting reaction mixture
  2. customThe reaction mixture was evaporated to dryness
  3. washwashed with saturated aqueous NaHCO3
  4. dry with materialThe organic layer was dried (MgSO4)
  5. filtrationfiltered
  6. customevaporated to dryness
  7. customThe residue was chromatographed on a silica gel column
  8. washeluting with 70% EtOAc/hexanes

Sources & evidence

ORD record
ord-1a147f3a78204c458e66445119b9c16f
Source dataset
uspto-grants-2015_12
Patent number
US09212164B2

Reaction notes

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