Boron tribromide → HCID 18735034, compound

HRID 844486Notes

Reaction equation

HRID 844486 reaction equation
[ClH:1].Cl.Cl.[NH2:4][CH:5]([CH2:21][NH:22][C@H:23]1[CH2:32][CH2:31][C:30]2[C:25](=[CH:26][CH:27]=[C:28]([O:33]C)[CH:29]=2)[C@H:24]1[CH2:35][C:36]1[CH:37]=[N:38][CH:39]=[CH:40][CH:41]=1)[CH2:6][CH2:7][CH2:8][CH2:9][NH:10][S:11]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[F:20])(=[O:13])=[O:12].B(Br)(Br)Br>C(Cl)Cl>[ClH:1].[ClH:1].[ClH:1].[NH2:4][CH:5]([CH2:21][NH:22][C@H:23]1[CH2:32][CH2:31][C:30]2[C:25](=[CH:26][CH:27]=[C:28]([OH:33])[CH:29]=2)[C@H:24]1[CH2:35][C:36]1[CH:37]=[N:38][CH:39]=[CH:40][CH:41]=1)[CH2:6][CH2:7][CH2:8][CH2:9][NH:10][S:11]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[F:20])(=[O:12])=[O:13]

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 18735036HCID 18735036, compound

Product 1

HCID 18735034HCID 18735034, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Aminotetralin sulfonamide 8 from the previous reaction (0.160 g, 0.246 mmol) was placed in a 50 mL round-bottom flask along with a stir bar. Methylene chloride (25 mL) was added and the slurry was cooled on an ice bath for several minutes. Boron tribromide in methylene chloride (1M, 1.25 mL, 1.25 mmol) was added to the reaction. The flask was flushed with argon, capped and allowed to warm up to ambient temperature and the mixture was stirred over 16 hours at which time the reaction was quenched by the addition of methanol (1 mL). The solvents were removed in vacuo and an additional aliquot of methanol was added to the resultant residue. Evaporation of the solvent from this mixture afforded crude product which was purified via reverse-phase chromatography (Bondapak C18, 3×(40×100 mm), gradient of H2O/CH3CN (+0.1% TFA)). The appropriate fractions were collected and lyophilized. The resultant material was subsequently treated with ethanolic-hydrogen chloride, followed by evaporation and drying under vacuum to give the phenolic product 9 as a white tris-hydrochloride salt (0.145 g, 0.228 mmol). NMR(d6-DMSO): δ 10.77 (br, 1H), 10.01 (br, 1H), 9.31 (br, 1H), 8.79 (d, 1H), 8.67 (m, 4H), 8.37 (d, 1H), 7.97 (m, 2H), 7.81 (dt, 1H), 7.72 (m, 1H), 7.52-7.36 (m, 2H), 6.57 (s, 1H), 6.22 (dd, 1H), 5.69 (d, 1H), 3.79 (m, 1H), 3.68-3.30 (m, 5H), 3.04 (m, 1H), 2.92-2.68 (m, 4H), 2.33-2.10 (m, 2H), 1.73-1.56 (m, 2H), 1.55-1.32 (m, 4H); MS: MH+=527 (Scheme 30).

Workup

  1. customwas placed in a 50 mL round-bottom flask along with a stir bar
  2. temperaturethe slurry was cooled on an ice bath for several minutes
  3. customThe flask was flushed with argon
  4. customcapped
  5. customwas quenched by the addition of methanol (1 mL)
  6. customThe solvents were removed in vacuo
  7. additionan additional aliquot of methanol was added to the resultant residue
  8. customEvaporation of the solvent from this mixture
  9. customafforded crude product which
  10. customwas purified via reverse-phase chromatography (Bondapak C18, 3×(40×100 mm), gradient of H2O/CH3CN (+0.1% TFA))
  11. customThe appropriate fractions were collected
  12. additionThe resultant material was subsequently treated with ethanolic-hydrogen chloride
  13. customfollowed by evaporation
  14. customdrying under vacuum

Sources & evidence

ORD record
ord-65b7cdbc2e4b4f9fb33ae4da3190370c
Source dataset
uspto-grants-2002_04
Patent number
US06380224B1

Reaction notes

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