Reaction #939034

ord-14d6c3e31a644494a5fee8bdc2274b4b

Reaction equation

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
budesonide
CCCCCCCCCCCCOC(=O)Cl
dodecyl chloroformate
CCN(CC)CC
Et3N
CCCCCCCCCCCCOC(=O)Cl
dodecyl chloroformate
CCN(CC)CC
Et3N
→
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.CCCCCCCCCCCCOC(=O)[O-]
budesonide dodecylcarbonate

Reactants

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
budesonide
CCCCCCCCCCCCOC(=O)Cl
dodecyl chloroformate
CCN(CC)CC
Et3N
CCCCCCCCCCCCOC(=O)Cl
dodecyl chloroformate
CCN(CC)CC
Et3N

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 dodecylcarbonate
  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 (750 mg, 1.74 mmol) in DCM (7.5 mL) was added dodecyl chloroformate (513 mL, 1.617 mmol) and Et3N (533 μL, 3.825 mmol) at room temperature. The reaction mixture was stirred at room temperature for 7 hours. During this 7 hours more dodecyl chloroformate (510 μL, 1.616 mmol) and Et3N (440 μL, 3.18 mmol) were added. The reaction was followed by HPLC. The reaction mixture 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 dodecylcarbonate. The product was purified by chromatography, eluted with Hexane:AcOEt=9:1 to 3:1 to provide 983 mg of 1:1 mixture of epimers (originated from budesonide) (96.78 area % purity on HPLC). 1H NMR (CDCl3) δ 0.80-2.25 (m, 45H), 2.36 (d, 1H, 13.4 Hz), 2.58 (t, 1H, 13.2 Hz), 4.19 (t, 2H, 6.7 Hz), 4.52 (bs, 1H), 4.6-5.2 (m, 5H), 6.03 (s, 1H), 6.30 (d, 1H, 10.1 Hz), 7.29 (d, 1H, 10.1 Hz). 13C NMR (CDCl3) δ 14.21, 14.38, 17.22, 17.35, 17.50, 17.78, 21.35, 22.94, 25.86, 28.83, 29.45, 29.60, 29.74, 29.80, 29.88, 30.57, 31.24, 32.16, 33.18, 33.68, 34.26, 35.26, 37.36, 41.17, 41.41, 44.24, 46.18, 47.61, 50.01, 53.14, 55.41, 55.52, 69.12, 69.18, 70.11, 70.22, 82.32, 83.57, 97.76, 98.62, 104.88, 108.63, 122.83, 128.24, 156.14, 169.81, 169.92, 186.74, 202.16 and 203.46. Mass spectrum (m/e) 643 (M+).

Source

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