Sodium Cyanide → HCID 18391511, compound

HRID 1586105Notes

Reaction equation

HRID 1586105 reaction equation
[C-:1]#[N:2].[Na+].[CH2:4]([O:6][C:7](=[O:34])[C@@H:8]1[CH2:12][C@H:11](OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:10][N:9]1[C:24]([O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:25])[CH3:5]>CS(C)=O.[Cl-].[Na+].O.O>[CH2:4]([O:6][C:7](=[O:34])[C@@H:8]1[CH2:12][C@@H:11]([C:1]#[N:2])[CH2:10][N:9]1[C:24]([O:26][CH2:27][C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)=[O:25])[CH3:5]

Participants

6

Reactant 2

HCID 8929Sodium Cyanide2×HCID 14804600HCID 14804600, compound

Product 1

HCID 18391511HCID 18391511, compoundYield 70.1%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

Finely powdered NaCN (0.49 g, 10 mmol) was suspended in a stirring mixture of 5 (3.0 g, 6.7 mmol) in DMSO (7 mL). The reaction flask was heated in an oil bath at 80° C. for 3 h, during which time the NaCN had completely dissolved and the reaction mixture had turned a deep orange color. After cooling to room temperature, the reaction was diluted with brine (3 mL) and H2O (4 mL), then extracted with Et2O (5×11 mL). The combined organic layers were dried (MgSO4) and concentrated to a yellow syrup which was purified by flash chromatography (silica gel, using 1:1 ethyl ether-petroleum ether) yielding 1.42 g (70%) of the N-CBZ-trans-4-cyano-L-proline ethyl ester as a colorless viscous oil: TLC Rf 0.22 (4:2 ethyl ether-petroleum ether); [α]24D -39° (c 1.05, CHCl3); 1H NMR (250 MHz, CDCl3) δ 7.38-7.27 (m, 5 H), 5.21-5.03 (m 2 H, PhCH2), 4.55-4.45 (m, 1 H, H-2), 4.21 (q, J=7.1 Hz, 1 H, CO2CH2CH3, one of two rotamers), 4.09-3.94 (m, 2 H, CO2CH2CH3 and H-5), 3.80-3.67 (m, 1 H, H-5), 3.35-3.21 (m, 1 H, H-4), 2.62-2.34 (m, 2 H, H-3), 1.28+1.13 (t, J=7.1 Hz, CO2CH2CH3, two rotamers); IR (CHCl3) 2995, 2900, 2250, 1740, 1705, 1420, 1355, 1195, 1125, 1020 cm-1 ; LRMS (CI, 70 eV, isobutane) m/e 303 (MH+, 66), 259 (44), 91 (100); HRMS (EI, 21 eV) m/e 302.1264 (302.1266 calcd for C16H18N2O4).

Workup

  1. dissolutionhad completely dissolved
  2. extractionextracted with Et2O (5×11 mL)
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. concentrationconcentrated to a yellow syrup which
  5. customwas purified by flash chromatography (silica gel, using 1:1 ethyl ether-petroleum ether)

Sources & evidence

ORD record
ord-9a1eb56252204955ba4a72ead877bf3a
Source dataset
uspto-grants-1999_08
Patent number
US05942537

Reaction notes

Loading…