Triethylamine → (1R,3aS,5aR,5bR,7aR,11aR,11bR,13aR,13bR)-3a-isocyanato-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)octadecahydro-1H-cyclopenta[a]chrysen-9(5bH)-one

HRID 338632Notes

Reaction equation

HRID 338632 reaction equation
[CH3:1][C@:2]12[C@@:19]3([CH3:20])[C@@H:10]([C@:11]4([CH3:24])[C@@H:16]([CH2:17][CH2:18]3)[C:15]([CH3:22])([CH3:21])[C:14](=[O:23])[CH2:13][CH2:12]4)[CH2:9][CH2:8][C@@H:7]1[C@H:6]1[C@H:25]([C:28]([CH3:30])=[CH2:29])[CH2:26]C[C@]1(C(O)=O)[CH2:4][CH2:3]2.C([N:36]([CH2:39]C)[CH2:37][CH3:38])C.P(N=[N+]=[N-])(=O)(OC1C=CC=CC=1)[O:42]C1C=CC=CC=1>O1CCOCC1>[N:36]([C@:37]12[CH2:38][CH2:26][C@@H:25]([C:28]([CH3:30])=[CH2:29])[C@@H:6]1[C@@H:7]1[C@@:2]([CH3:1])([CH2:3][CH2:4]2)[C@@:19]2([CH3:20])[C@@H:10]([C@:11]3([CH3:24])[C@@H:16]([CH2:17][CH2:18]2)[C:15]([CH3:21])([CH3:22])[C:14](=[O:23])[CH2:13][CH2:12]3)[CH2:9][CH2:8]1)=[C:39]=[O:42]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 122844(+)-Betulonic acidHCID 123414Diphenylphosphoryl azide

Product 1

HCID 25426274(1R,3aS,5aR,5bR,7aR,11aR,11bR,13aR,13bR)-3a-isocyanato-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)octadecahydro-1H-cyclopenta[a]chrysen-9(5bH)-oneYield 63.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of (1R,3aS,5aR,5bR,7aR,11aR,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-9-oxo-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysene-3a-carboxylic acid (16.41 g, 36.1 mmol) in 1,4-dioxane (200 mL) was added triethylamine (15.09 mL, 108 mmol) and diphenyl phosphorazidate (11.67 mL, 54.2 mmol). The mixture was heated to reflux for 18.5 h, then was cooled to rt and concentrated under reduced pressure. The residue was split into two portions and was purified using a 0-15% ethyl acetate in hexanes gradient and a Thomson 240 g silica gel column to purify each portion. The fractions containing the expected product were combined and concentrated under reduced pressure to give (1R,3aS,5aR,5bR,7aR,11aR,11bR,13aR,13bR)-3a-isocyanato-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)octadecahydro-1H-cyclopenta[a]chrysen-9(5bH)-one (10.3 g, 22.80 mmol, 63.2% yield) as an off-white foam. 1H NMR (400 MHz, chloroform-d) δ=4.75 (d, J=2.0 Hz, 1H), 4.66-4.63 (m, 1H), 2.60-2.36 (m, 4H), 2.17-2.04 (m, 1H), 1.69 (s, 3H), 1.10 (s, 3H), 1.08 (s, 3H), 1.04 (s, 3H), 0.95 (s, 6H), 2.01-0.71 (m, 20H).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 18.5 h
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was split into two portions
  5. customwas purified
  6. customa Thomson 240 g silica gel column to purify each portion
  7. additionThe fractions containing the expected product
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-708e1e605cfe4713a8bd05cd8c4d0724
Source dataset
uspto-grants-2014_11
Patent number
US08889854B2

Reaction notes

Loading…