Hydrochloric Acid → 7-Bromo-5-(2-fluoro-phenyl)-3-methyl-1,3-dihydro-benzo[e][1,4]diazepin-2-one

HRID 1435816ノート

反応式

HRID 1435816 の反応式
C(OC(=O)[NH:7][CH:8]([C:10](=[O:28])[NH:11][C:12]1[CH:17]=[CH:16][C:15]([Br:18])=[CH:14][C:13]=1[C:19](=O)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[F:26])[CH3:9])(C)(C)C.Cl>C(Cl)(Cl)Cl>[Br:18][C:15]1[CH:16]=[CH:17][C:12]2[NH:11][C:10](=[O:28])[CH:8]([CH3:9])[N:7]=[C:19]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[F:26])[C:13]=2[CH:14]=1

参加物

4

反応物 2

HCID 313Hydrochloric AcidHCID 68523676{1-[4-Bromo-2-(2-fluorobenzoyl)-phenylcarbamoyl]-ethyl)-carbamic acid tert-butyl ester

生成物 1

HCID 685254147-Bromo-5-(2-fluoro-phenyl)-3-methyl-1,3-dihydro-benzo[e][1,4]diazepin-2-one収率 82%

試薬・触媒・溶媒 1

HCID 6212Chloroform溶媒

実験手順

To a stirred solution of the benzophenone 136 (30 g, 64.4 mmol) in CHCl3 (300 mL) at rt, hydrogen chloride gas was added slowly. After 20 min, the addition was stopped and the solution was allowed to stir overnight at rt. The reaction mixture was then washed with a saturated solution of sodium bicarbonate (2×70 mL) and water (2×70 mL). The organic layer was concentrated under reduced pressure. The residual oil was dissolved in methanol-water (1:1, 300 mL) and the pH was adjusted to 8.5 by the addition of aq sodium hydroxide (1 N). The reaction mixture was allowed to stir for 10 h at rt. The solution was then concentrated under reduced pressure and water (100 mL) was added. The solution was extracted with CH2Cl2 (3×50 mL), and the organic layer was dried (Na2SO4) and concentrated under reduced pressure. The crude solid 137 was purified by recrystallization from methanol/water to provided 137(18.2 g, 82%). mp 183-185° C.; IR (KBr, cm−1) 2928, 1694, 1611, 1479, 1450, 1377, 1315; 1H NMR(CDCl3) δ 9.50 (bs, 1H), 7.62-7.65 (m, 2H), 7.50 (q, J=6.5 Hz, 1H), 7.40 (d, J=2.0 Hz, 1H), 7.29 (t, J=7.5 Hz 1H) 7.15 (d, J=8.6 Hz, 1H), 7.11 (t, J=8.9 Hz, 1H), 3.84 (q, J=6.5 Hz, 1H), 1.82 (d, J=6.5 Hz, 3H); MS (EI) m/e (relative intensity) 348 (M++1, 23), 347 (M+, 38), 346 (24), 345 (36), 329 (19), 327 (20), 307 (40), 306 (41), 305(100), 304 (37), 303 (63); [α]26D=−169.1 (c 0.71, EtOAc).

後処理

  1. additionthe addition
  2. washThe reaction mixture was then washed with a saturated solution of sodium bicarbonate (2×70 mL) and water (2×70 mL)
  3. concentrationThe organic layer was concentrated under reduced pressure
  4. dissolutionThe residual oil was dissolved in methanol-water (1:1, 300 mL)
  5. additionthe pH was adjusted to 8.5 by the addition of aq sodium hydroxide (1 N)
  6. stirringto stir for 10 h at rt
  7. concentrationThe solution was then concentrated under reduced pressure and water (100 mL)
  8. additionwas added
  9. extractionThe solution was extracted with CH2Cl2 (3×50 mL)
  10. dry with materialthe organic layer was dried (Na2SO4)
  11. concentrationconcentrated under reduced pressure
  12. customThe crude solid 137 was purified by recrystallization from methanol/water

出典と根拠

ORDレコード
ord-0230b66dff4f4fae99df00fd686caa85
出典データセット
uspto-grants-2009_11
特許番号
US07618958B2

反応ノート

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