Ethyl Acetate → tert-Butyl 9,10-dichloro-6-(2-hydroxyethyl)-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate

HRID 1356326Notes

Reaction equation

HRID 1356326 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]([CH2:11][C:12](OCC)=[O:13])[C:6]3[CH2:17][CH2:18][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:20][CH2:21][C:5]=3[C:4]=2[C:3]=1[Cl:29].[Li+].[BH4-].[OH-].[Na+].CCOC(C)=O>C1COCC1.O>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]([CH2:11][CH2:12][OH:13])[C:6]3[CH2:17][CH2:18][N:19]([C:22]([O:24][C:25]([CH3:27])([CH3:26])[CH3:28])=[O:23])[CH2:20][CH2:21][C:5]=3[C:4]=2[C:3]=1[Cl:29]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 4148881Lithium borohydrideHCID 22396818tert-Butyl 9,10-dichloro-6-(2-ethoxy-2-oxoethyl)-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate

Product 1

HCID 22396738tert-Butyl 9,10-dichloro-6-(2-hydroxyethyl)-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylateYield 21%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of tert-butyl 9,10-dichloro-6-(2-ethoxy-2-oxoethyl)-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (1.0 g, 2.3 mmol) in dry THF (10 mL) was cooled to 0° C. Then, LiBH4 (0.15 g, 6.8 mmol) was added and the reaction was allowed to warm slowly to rt. After 4 h, the reaction was diluted with H2O followed by addition of 10% aqueous NaOH and extraction with EtOAc (3×50 mL). The combined organic extracts were washed with brine, dried over Na2SO4, decanted, and concentrated. The crude product was purified by column chromatography (Biotage, 40M, SIM) with heptane/EtOAc (1:1) followed by crystallization from EtOAc/heptane gave 0.19 g (21%) of a white solid: mp 174.5-176.0° C.; IR (diffuse reflectance) 3419, 1662, 1466, 1447, 1424, 1370, 1359, 1275, 1248, 1170, 1157, 1120, 1078, 933, 799 cm−1; MS (EI) m/z 398 (M+), 400, 398, 344, 342, 341, 268, 86, 84, 57, 51; Anal. Calcd for C19H24Cl2N2O3: C, 57.15; H, 6.06; N, 7.01; found: C, 57.13; H, 6.13; N, 6.95.

Workup

  1. washThe combined organic extracts were washed with brine
  2. dry with materialdried over Na2SO4
  3. customdecanted
  4. concentrationconcentrated
  5. customThe crude product was purified by column chromatography (Biotage, 40M, SIM) with heptane/EtOAc (1:1)
  6. customfollowed by crystallization from EtOAc/heptane

Sources & evidence

ORD record
ord-fd8b6c8dc23e49eb98a2cd9b0c4c7562
Source dataset
uspto-grants-2003_07
Patent number
US06586421B2

Reaction notes

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