Ethyl Acetate → HCID 22396797, compound

HRID 2307009Notes

Reaction equation

HRID 2307009 reaction equation
[Cl:1][C:2]1[C:3]([Cl:29])=[CH:4][C:5]2[C:6]3[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17][C:7]=3[N:8]([CH2:11][C:12](OCC)=[O:13])[C:9]=2[CH:10]=1.[Li+].[BH4-].[OH-].[Na+].CCOC(C)=O>C1COCC1.O>[Cl:1][C:2]1[C:3]([Cl:29])=[CH:4][C:5]2[C:6]3[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:27])([CH3:26])[CH3:28])=[O:23])[CH2:18][CH2:17][C:7]=3[N:8]([CH2:11][CH2:12][OH:13])[C:9]=2[CH:10]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 4148881Lithium borohydrideHCID 22396677HCID 22396677, compound

Product 1

HCID 22396797HCID 22396797, compoundYield 59.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution tert-butyl 8,9-dichloro-6-(2-ethoxy-2-oxoethyl)-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (0.95 g, 2.15 mmol) in dry THF (10 mL) was cooled to 0° C. Then, LiBH4 (0.14 g, 6.43 mmol) was added and the reaction was allowed to warm slowly to rt. After 17 h, the reaction was diluted with H2O (50 mL) followed by addition of 10% aqueous NaOH (10 mL) 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 first purified by two column chromatographies (Biotage, 40M) with heptane/EtOAc (1:1) and (Biotage, 40S) with heptane/EtOAc (2:1) to give 0.51 g of impure product. Finally, crystallization from Et2O/heptane gave 0.45 g (52%) of pale yellow crystals: mp 130.5-133° C.; IR (diffuse reflectance) 3469, 2976, 2937, 2869, 1676, 1477, 1449, 1415, 1366, 1342, 1240, 1219, 1172, 1164, 853 cm−1; MS (EI) m/z 398 (M+), 400, 398, 342, 341, 270, 268, 86, 84, 57, 51; Anal. Calcd for C19H24Cl2N2O3: C, 57.15; H, 6.06; N, 7.01; found: C, 57.24; H, 6.19; 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 first purified by two column chromatographies (Biotage, 40M) with heptane/EtOAc (1:1) and (Biotage, 40S) with heptane/EtOAc (2:1)

Sources & evidence

ORD record
ord-3eebdf73e948414db08a2629144599e0
Source dataset
uspto-grants-2004_12
Patent number
US06828314B2

Reaction notes

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