Dichloromethane → HCID 52913223, compound

HRID 2036704Notes

Reaction equation

HRID 2036704 reaction equation
C[O:2][C:3]1[CH:4]=[C:5]([S:9]([C:12]2[CH:20]=[CH:19][C:18]3[N:17]([CH3:21])[C:16]4[CH2:22][CH:23]5[NH:27][CH:26]([C:15]=4[C:14]=3[C:13]=2C(OC(C)(C)C)=O)[CH2:25][CH2:24]5)(=[O:11])=[O:10])[CH:6]=[CH:7][CH:8]=1.B(Br)(Br)Br.[Cl:39]CCl>>[ClH:39].[OH:2][C:3]1[CH:4]=[C:5]([S:9]([C:12]2[CH:13]=[C:14]3[C:18](=[CH:19][CH:20]=2)[N:17]([CH3:21])[C:16]2[CH2:22][CH:23]4[NH:27][CH:26]([C:15]3=2)[CH2:25][CH2:24]4)(=[O:11])=[O:10])[CH:6]=[CH:7][CH:8]=1

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 25134Boron tribromideHCID 67085605HCID 67085605, compound

Product 1

HCID 52913223HCID 52913223, compound

Procedure

A solution of the product of Example 41, step A (86 mg, 0.21 mmol) in dichloromethane (2.5 mL) at 0° C. was treated with boron tribromide (2.5 mL, 2.1 mmol). The reaction was stirred for 4 h then quenched with methanol followed by saturated sodium bicarbonate. The mixture was extracted with dichloromethane and the organic extract concentrated in vacuo. The residue was purified by flash column chromatography (SiO2, 95:5 dichloromethane/methanol) and the residue dissolved in a minimum of methanol. The solution was treated with 1.25 M HCl in methanol (2 mL) then concentrated in vacuo to give 2-(3-hydroxyphenyl)sulfonyl-5-methyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole hydrochloride (21 mg, 23%, AUC HPLC >99%) as an off-white solid: mp 208-212° C.; 1H NMR (DMSO-d6, 300 MHz) δ 10.20 (s, 1H), 8.90-9.40 (m, 2H), 8.32 (s, 1H), 7.60-7.67 (m, 2H), 7.29-7.39 (m, 2H), 7.25 (s, 1H), 6.98 (s, 1H), 5.32-5.39 (br s, 1H), 4.46 (br s, 1H), 3.70 (s, 3H), 3.37-3.39 (m, 1H), 3.01 (d, J=17.0 Hz, 1H), 2.26 (br s, 2H), 2.06-2.12 (m, 1H), 1.72-1.86 (m, 1H). ESI MS m/z 369 [M+H]+

Workup

  1. customthen quenched with methanol
  2. extractionThe mixture was extracted with dichloromethane
  3. extractionthe organic extract
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash column chromatography (SiO2, 95:5 dichloromethane/methanol)
  6. dissolutionthe residue dissolved in a minimum of methanol
  7. additionThe solution was treated with 1.25 M HCl in methanol (2 mL)
  8. concentrationthen concentrated in vacuo

Sources & evidence

ORD record
ord-f400baac963c48158843aacaab12f05a
Source dataset
uspto-grants-2013_11
Patent number
US08575186B2

Reaction notes

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