Water → Budesonide hexadecylcarbonate

HRID 2093303Notes

Reaction equation

HRID 2093303 reaction equation
[CH3:1][CH2:2][CH2:3][CH:4]1[O:24][C@:23]2([C:25]([CH2:27][OH:28])=[O:26])[C@@H:6]([CH2:7][C@@H:8]3[C@:22]2([CH3:29])[CH2:21][C@H:20]([OH:30])[C@H:19]2[C@H:9]3[CH2:10][CH2:11][C:12]3[C@:18]2([CH3:31])[CH:17]=[CH:16][C:14](=[O:15])[CH:13]=3)[O:5]1.ClC([O-])=[O:34].CCN(CC)CC.O>C(Cl)Cl>[CH3:1][CH2:2][CH2:3][CH:4]1[O:24][C@:23]2([C:25]([CH2:27][OH:28])=[O:26])[C@@H:6]([CH2:7][C@@H:8]3[C@:22]2([CH3:29])[CH2:21][C@H:20]([OH:30])[C@H:19]2[C@H:9]3[CH2:10][CH2:11][C:12]3[C@:18]2([CH3:31])[CH:17]=[CH:16][C:14](=[O:15])[CH:13]=3)[O:5]1.[CH2:23]([O:24][C:4](=[O:5])[O-:34])[CH2:6][CH2:7][CH2:8][CH2:22][CH2:21][CH2:20][CH2:19][CH2:9][CH2:10][CH2:11][CH2:12][CH2:18][CH2:17][CH2:16][CH3:14]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 5281004Budesonide2×HCID 21226386Carbonochloridate

Product 1

HCID 86589554Budesonide hexadecylcarbonate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To the solution of budesonide (431 mg, 1.0 mmol) in DCM (4.5 mL) was added heaxdecyl chloroformate (655 μL, 2.0 mmol) and Et3N (512 μL, 3.7 mmol) at room temperature. After 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 hexadecylcarbonate. The product was purified by chromatography, eluted with Hexane:AcOEt=9:1 to 3:1 to provide 432 mg of 1:1 mixture of epimers (originated from budesonide) (99.38 area % purity on HPLC). 1H NMR (CDCl3) δ 0.80-2.40 (m, 53H), 2.56 (dt, 1H, 13.1 and 4.6 Hz), 4.30 (t, 2H, 6.7 Hz), 4.5-5.2 (m, 7H), 6.00 (s, 1H), 6.26 (d, 1H, 10.1 Hz), 7.3 (d, 1H, 10.1 Hz). 13C NMR (CDCl3) δ 14.16, 14.18, 14.34, 17.10, 17.27, 17.39, 17.71, 21.21, 22.88, 25.81, 28.79, 29.41, 29.56, 29.70, 29.76, 29.87, 30.54, 31.19, 32.11, 33.08, 33.59, 34.23, 35.19, 37.28, 40.68, 40.98, 44.37, 46.08, 47.52, 50.00, 53.07, 55.39, 55.49, 68.98, 69.73, 69.83, 69.95, 70.04, 82.10, 83.38, 97.71, 98.58, 104.70, 108.51, 122.57, 127.91, 155.08, 156.85, 170.48, 170.59, 186.84, 186.88, 202.10 and 203.38. Mass spectrum (m/e) 699 (M+).

Workup

  1. customAfter reaction mixture
  2. extractionthe aqueous phase was extracted with DCM (10 mL)
  3. washThe combined organic phases were washed with water (10 mL) and brine (10 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto provide crude budesonide hexadecylcarbonate
  8. customThe product was purified by chromatography
  9. washeluted with Hexane
  10. customAcOEt=9:1 to 3:1 to provide

Sources & evidence

ORD record
ord-f6aa347500a7441981ed7628912dc3af
Source dataset
uspto-grants-2013_05
Patent number
US08445470B2

Reaction notes

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