Reaction #939036

ord-4940ebc2f6e447f89de7b149cf572928

Reaction equation

CCCC1O[C@@H]2C[C@H]3[C@@H]4CCC5=CC(=O)C=C[C@]5(C)[C@H]4[C@@H](O)C[C@]3(C)[C@]2(C(=O)CO)O1
budesonide
CCCCCCCCCCOC(=O)Cl
decyl chloroformate
CCN(CC)CC
Et3N
O
water
CCCC1O[C@@H]2C[C@H]3[C@@H]4CCC5=CC(=O)C=C[C@]5(C)[C@H]4[C@@H](O)C[C@]3(C)[C@]2(C(=O)CO)O1
budesonide
→
CCCC1O[C@@H]2C[C@H]3[C@@H]4CCC5=CC(=O)C=C[C@]5(C)[C@H]4[C@@H](O)C[C@]3(C)[C@]2(C(=O)CO)O1.CCCCCCCCCCOC(=O)[O-]
budesonide decylcarbonate

Reactants

CCCC1O[C@@H]2C[C@H]3[C@@H]4CCC5=CC(=O)C=C[C@]5(C)[C@H]4[C@@H](O)C[C@]3(C)[C@]2(C(=O)CO)O1
budesonide
CCCCCCCCCCOC(=O)Cl
decyl chloroformate
CCN(CC)CC
Et3N
O
water
CCCC1O[C@@H]2C[C@H]3[C@@H]4CCC5=CC(=O)C=C[C@]5(C)[C@H]4[C@@H](O)C[C@]3(C)[C@]2(C(=O)CO)O1
budesonide

Reagents

None

Solvents

ClCCl
DCM
ClCCl
DCM

Conditions

Detailed conditions
See reaction.notes.procedure_details.

Workup

  1. 1
    Extractionthe aqueous phase was extracted with DCM (10 mL)
  2. 2
    WashThe combined organic phases were washed with water (10 mL) and brine (10 mL)
  3. 3
    Dryingdried over Na2SO4
  4. 4
    Filtrationfiltered
  5. 5
    Concentrationconcentrated in vacuo
  6. 6
    Otherto provide crude budesonide decylcarbonate
  7. 7
    OtherThe product was purified by chromatography
  8. 8
    Washeluted with Hexane
  9. 9
    OtherAcOEt=9:1 to 3:1 to provide

Procedure

To the solution of budesonide (431 mg, 1.0 mmol) in DCM (4.5 mL) was added decyl chloroformate (460 μL, 2.0 mmol) and Et3N (512 μL, 3.7 mmol) at room temperature. After the reaction mixture was stirred at room temperature over night, it was poured into water (20 mL) and DCM (10 mL); the aqueous phase was extracted with DCM (10 mL). The combined organic phases were washed with water (10 mL) and brine (10 mL), dried over Na2SO4, filtered, and concentrated in vacuo to provide crude budesonide decylcarbonate. The product was purified by chromatography, eluted with Hexane:AcOEt=9:1 to 3:1 to provide 348 mg of 1:1 mixture of epimers (originated from budesonide) (99.22 area % purity on HPLC). 1H NMR (CDCl3) δ 0.85-2.24 (m, 42H), 2.36 (dd, 1H, 13.4 and 2.9 Hz), 2.59 (dt, 1H, 13.5 and 4.5 Hz), 4.18 (t, 1H, 6.7 Hz), 4.51 (s, 1H), 4.6-5.2 (m, 5H), 6.03 (s, 1H), 6.30 (d, 1H, 10.1 Hz), 7.49 (d, 1H, 10.1 Hz). 13C NMR (CDCl3) δ 14.14, 14.17, 14.31, 17.06, 17.24, 17.36, 17.68, 21.19, 22.83, 25.78, 28.76, 29.37, 29.40, 29.66, 30.52, 31.16, 32.04, 33.05, 33.56, 34.22, 35.16, 37.25, 40.58, 40.89, 44.38, 46.06, 47.49, 49.98, 53.05, 55.38, 55.48, 68.90, 68.94, 69.65, 69.75, 69.92, 70.01, 82.05, 83.34, 97.69, 98.56, 104.65, 108.47, 122.51, 127.84, 155.04, 156.96, 170.61, 170.71, 186.84, 186.89, 202.08 and 203.37. Mass spectrum (m/e) 615 (M+).

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: US07253156B2uspto-grants-2007_08