Trifluoroacetic acid → HCID 22396888, compound

HRID 2306997Notes

Reaction equation

HRID 2306997 reaction equation
[Cl:1][C:2]1[C:3]([Cl:32])=[CH:4][C:5]2[C:6]3[CH2:24][CH2:23][N:22](C(OC(C)(C)C)=O)[CH2:21][CH2:20][C:7]=3[N:8]([CH2:11][CH2:12][CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:9]=2[CH:10]=1.C(O)(C(F)(F)F)=O.[OH-].[Na+]>C(Cl)Cl>[ClH:1].[Cl:1][C:2]1[C:3]([Cl:32])=[CH:4][C:5]2[C:6]3[CH2:24][CH2:23][NH:22][CH2:21][CH2:20][C:7]=3[N:8]([CH2:11][CH2:12][CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:9]=2[CH:10]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 22396651HCID 22396651, compound

Product 1

HCID 22396888HCID 22396888, compoundYield 115%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 8,9-dichloro-6-(3-phenylpropyl)-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (0.20 g, 0.42 mmol) in CH2Cl2 (5 mL), TFA (0.65 mL, 8.4 mmol) was added while stirring at rt. After 4 h, the reaction was made basic with 10% aqueous NaOH, then extracted with CH2Cl2 (3×15 mL). The combined organic layers were washed with brine, dried over Na2SO4, decanted, and concentrated to 0.12 g of crude material. After the hydrochloride salt was prepared, it was further purified by recrystallization from MeOH/EtOAc to give 99 mg (57%) of a white solid: mp 148.0-150.5° C.; 1H NMR (300 MHz, DMSO) δ 9.26 (br s, 2H), 7.75 (d, J=8.7 Hz, 2H), 7.28 (m, 2H), 7.20 (m, 3H), 4.19 (m, 2H), 3.19 (m, 2H), 3.08 (m, 2H), 2.61 (m, 2H), 1.89 (pentet, J=7.5 Hz, 2H); 13C NMR (400 MHz, DMSO) δ 141.0, 138.4, 134.0, 128.2, 128.1, 126.5, 125.8, 123.0, 121.4, 118.7, 111.3, 110.2, 45.8, 44.0, 42.3, 31.9, 31.5, 22.5, 20.2; IR (diffuse reflectance) 3021, 2997, 2970, 2953, 2888, 2850, 2825, 2812, 2760, 2709, 2632, 1473, 1421, 1106, 700 cm−1; MS (EI) m/z 374, 372 (M+), 332, 331, 330, 228, 226, 91, 86, 84.

Workup

  1. extractionextracted with CH2Cl2 (3×15 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over Na2SO4
  4. customdecanted
  5. concentrationconcentrated to 0.12 g of crude material
  6. customAfter the hydrochloride salt was prepared
  7. customit was further purified by recrystallization from MeOH/EtOAc

Sources & evidence

ORD record
ord-479136f7004b4b4d9759d37f8fc3ad2a
Source dataset
uspto-grants-2004_12
Patent number
US06828314B2

Reaction notes

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