Triethylamine → HCID 69269265, compound

HRID 349814Notes

Reaction equation

HRID 349814 reaction equation
[C:1]([O:5][C:6](=[O:23])[CH2:7][C@H:8]([CH2:12][C@H:13]([CH3:22])[CH2:14][CH2:15][CH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1)C(O)=O)(C)(C)C.C([N:26](CC)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1>C1(C)C=CC=CC=1>[CH3:1][O:5][C:6](=[O:23])[CH2:7][C@@H:8]([NH2:26])[CH2:12][C@H:13]([CH3:22])[CH2:14][CH2:15][CH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 69267907HCID 69267907, compound

Product 1

HCID 69269265HCID 69269265, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A flask was charged with 2.19 g (6.71 mmol) of (S)-2-((R)-4-cyclohexyl-2-methyl-butyl)-succinic acid 4-tert-butyl ester, 40 mL of toluene, 0.935 mL (6.71 mmol) of triethylamine, and 1.45 mL (6.71 mmol) of diphenylphosphorylazide. The mixture was stirred for 15 minutes at room temperature and then heated to 110° C. and stirred for 6 hours. The toluene was removed under reduced pressure, and the residue was taken up in diethyl ether. The ether layer was washed with 3M HCl aq., water, and brine. The ether was removed under reduced pressure, and the crude isocyanate was taken up in 3 M HCl aq. and heated at reflux for 8 hours. The water was removed under reduced pressure, and the residue was triturated with ether. This provided 1.45 g of an impure white solid. A portion of the white solid was dissolved in methanol, and HCl gas was bubbled through for 15 minutes. The acidic solution was stirred 2 hours. The methanol was removed under reduced pressure, and the crude ester was purified by column chromatography (4:1 dichloromethane: methanol). This gave 0.356 g of the pure ester: 1H NMR (400 MHz, CDCl3) δ ppm 0.85 (m, 2 H) 0.88 (d, J=8.00 Hz, 3 H) 1.15 (m, 6 H) 1.26 (m, 1 H) 1.36 (ddd, J=13.73, 9.21, 4.64 Hz, 1 H) 1.51 (m, 1 H) 1.65 (m, 7 H) 2.28 (dd, J=15.86, 8.78 Hz, 1 H) 2.43 (dd, J=16.0, 4.00 Hz, 1 H) 3.28 (m, J=8.97, 8.97, 4.39, 4.27 Hz, 1 H) 3.69 (s, 3H). MS (APCl) m+1/z=256.

Workup

  1. temperatureheated to 110° C.
  2. stirringstirred for 6 hours
  3. customThe toluene was removed under reduced pressure
  4. washThe ether layer was washed with 3M HCl aq., water, and brine
  5. customThe ether was removed under reduced pressure
  6. temperatureheated
  7. temperatureat reflux for 8 hours
  8. customThe water was removed under reduced pressure
  9. customthe residue was triturated with ether
  10. dissolutionA portion of the white solid was dissolved in methanol
  11. customHCl gas was bubbled through for 15 minutes
  12. stirringThe acidic solution was stirred 2 hours
  13. customThe methanol was removed under reduced pressure
  14. customthe crude ester was purified by column chromatography (4:1 dichloromethane: methanol)

Sources & evidence

ORD record
ord-11c96c70d14c4a2a8e10f98022a04d22
Source dataset
uspto-grants-2007_02
Patent number
US07179934B2

Reaction notes

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