Ethanol → HCID 59382925, compound

HRID 2355443Notes

Reaction equation

HRID 2355443 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][CH:14]1[CH2:19][CH2:18][CH:17]([CH3:20])[CH2:16][CH2:15]1)[C:10](O)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].C[CH2:22][N:23]=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.CN.CCO>C(Cl)Cl>[CH3:22][NH:23][C:10]([C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH2:13][CH:14]1[CH2:19][CH2:18][CH:17]([CH3:20])[CH2:16][CH2:15]1)=[O:11]

Participants

8

Reactant 6

HCID 702EthanolHCID 6329MethylamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57544653HCID 57544653, compound

Product 1

HCID 59382925HCID 59382925, compoundYield 47%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of (S)-2-(tert-butoxycarbonylamino)-3-(4-methylcyclohexyl)propanoic acid (2.080 g, 7.29 mmol, 1.0 equiv), EDC.HCl (3.308 g, 2.37 equiv), HOBt (1.752 g, 1.78 equiv), DIEA (7.6 mL, 6 equiv) and 33% wt. methylamine in EtOH (2.771 g, 4 equiv) in CH2Cl2 (80 mL) was stirred at rt for 21 h. The solvents were removed in vacuo and 1 N aq HCl (200 mL) was added. The mixture was extracted with EtOAc (3×). The combined organic extracts were washed with brine and dried over Na2SO4. After the solvents were removed in vacuo, the residue was purified by reversed-phase HPLC (Phenomenex® Luna 5μ C18(2) 100 A, 250×21.20 mm, 5 micron, 10%→90% CH3CN/H2O, 0.1% CF3COOH over 13 min and then 90% CH3CN/H2O, 0.1% CF3COOH over 3.5 min, flow rate 25 mL/min) to give tert-butyl (S)-1-(methylcarbamoyl)-2-(4-methylcyclohexyl)ethylcarbamate (1.0167 g, 47%). LC-MS (3 min) tR=1.72 min, m/z 321 (M+Na+), 243, 199; 1H NMR (400 MHz, CDCl3) δ 6.27 (br s, 1H), 4.91 (br s, 1H), 4.11-4.07 (m, 1H), 2.802, 2.798 (d, J=4.8 Hz, 3H), 1.85-1.20 (m, 21H), 0.886, 0.851 (d, J=6.4 Hz, 3H).

Workup

  1. customThe solvents were removed in vacuo and 1 N aq HCl (200 mL)
  2. additionwas added
  3. extractionThe mixture was extracted with EtOAc (3×)
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over Na2SO4
  6. customAfter the solvents were removed in vacuo
  7. customthe residue was purified by reversed-phase HPLC (Phenomenex® Luna 5μ C18(2) 100 A, 250×21.20 mm, 5 micron, 10%
  8. customover 13 min
  9. wait90% CH3CN/H2O, 0.1% CF3COOH over 3.5 min

Sources & evidence

ORD record
ord-55a3f08a5c184dafb07219720fdb2d8e
Source dataset
uspto-grants-2010_07
Patent number
US07754737B2

Reaction notes

Loading…