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

HRID 75264Notes

Reaction equation

HRID 75264 reaction equation
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

Participants

4

Reactant 2

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

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, 1 H), 7.62-7.65 (m, 2 H), 7.50 (q, J=6.5 Hz, 1H), 7.40 (d, J=2.0 Hz, 1 H), 7.29 (t, J=7.5 Hz 1 H) 7.15 (d, J=8.6 Hz, 1 H), 7.11 (t, J=8.9 Hz, 1 H), 3.84 (q, J=6.5 Hz, 1 H), 1.82 (d, J=6.5 Hz, 3 H); 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).

Workup

  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

Sources & evidence

ORD record
ord-fd9f4b725e714ab5afcd32272997ecba
Source dataset
uspto-grants-2014_09
Patent number
US08835424B2

Reaction notes

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