تفاعل #939037

ord-925a102b075c4644b6f9c3d979060e76

معادلة التفاعل

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
CCCCN=C=O
butyl isocyanate
CCCCN=C=O
butyl isocyanate
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.CCCCNC(=O)[O-]
budesonide butylcarbamate

المذيبات

ظروف التفاعل

الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    استخلاصthe aqueous phase was extracted with DCM (10 mL)
  2. 2
    غسيلThe combined organic phases were washed with water (10 mL) and brine (10 mL)
  3. 3
    تجفيفdried over Na2SO4
  4. 4
    ترشيحfiltered
  5. 5
    تركيزconcentrated in vacuo
  6. 6
    أخرىto provide crude budesonide butylcarbamate
  7. 7
    أخرىThe product was purified by chromatography
  8. 8
    غسيلeluted with Hexane
  9. 9
    أخرىAcOEt=9:1 to 3:1 to provide

الإجراء التجريبي

To the solution of budesonide (500 mg, 1.16 mmol) in DCM (5.0 mL) was added butyl isocyanate (144 μL, 1.28 mmol) and DMAP (312 mg, 2.55 mmol) at room temperature. The reaction mixture was stirred at room temperature for 24 hours. During this 24 hours more butyl isocyanate (72 μL, 0.64 mmol) and DMAP (156 mg, 1.27 mmol). 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 butylcarbamate. The product was purified by chromatography, eluted with Hexane: AcOEt=9:1 to 3:1 to provide 560 mg of 1:1 mixture of epimers (originated from budesonide) (99.22 area % purity on HPLC). 1H NMR (CDCl3) δ 0.82-2.7 (m, 30H), 3.06-3.20 (m, 3H), 4.45 (m, 1H), 4.58 (t, 1H, 4.5 Hz), 4.75-5.36 (m, 5H), 5.99 (s, 1H), 6.24 (d, 1H, 10.1 Hz), 7.29 (d, 1H, 10.1 Hz). 13C NMR (CDCl3) δ 13.98, 14.08, 14.22, 17.09, 17.30, 17.37, 17.73, 20.09, 20.28, 21.26, 30.56, 31.22, 32.11, 32.59, 33.13, 33.65, 34.27, 35.23, 37.34, 40.30, 40.73, 40.99, 41.17, 44.37, 46.09, 47.49, 50.01, 53.15, 55.43, 55.52, 67.82, 69.82, 69.93, 82.11, 83.37, 97.84, 98.75, 104.66, 108.43, 122.61, 127.97, 155.94, 156.03, 156.79, 170.45, 170.56, 186.95, 203.89 and 205.21.

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US07253156B2uspto-grants-2007_08