Ethyl Acetate → HCID 22396830, compound

HRID 2307013Notes

Reaction equation

HRID 2307013 reaction equation
[Cl:1][C:2]1[C:10]2[N:9]([CH2:11][C:12](OCC)=[O:13])[C:8]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:7]=3[C:6]=2[CH:5]=[C:4]([Cl:29])[CH:3]=1.[Li+].[BH4-].[OH-].[Na+].CCOC(C)=O>C1COCC1.O>[Cl:1][C:2]1[C:10]2[N:9]([CH2:11][CH2:12][OH:13])[C:8]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:7]=3[C:6]=2[CH:5]=[C:4]([Cl:29])[CH:3]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 4148881Lithium borohydride2×HCID 22396583HCID 22396583, compound

Product 1

HCID 22396830HCID 22396830, compoundYield 87.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution tert-butyl 7,9-dichloro-6-(2-ethoxy-2-oxoethyl)-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (3.00 g, 6.80 mmol) in dry THF (30 mL) was cooled to 0° C. Then, LiBH4 (0.44 g, 20.2 mmol) was added and the reaction was allowed to warm slowly to rt. After 18 h, additional LiBH4 (0.44 g, 20.2 mmol) was added. After an additional 24 h, the reaction was diluted with H2O followed by addition of 10% aqueous NaOH and extraction with EtOAc. The combined organic extracts were washed with brine, dried over Na2SO4, decanted, and concentrated. The crude product was first purified by column chromatography (Biotage 40M, SIM) with heptane/EtOAc (1:1) to give 2.37 g of impure product. Then, crystallization from EtOAc/heptane gave 2.21 g (82%) of ivory crystals: mp 183-184° C.; IR (diffuse reflectance) 1693, 1658, 1468, 1448, 1433, 1406, 1380, 1370, 1347, 1323, 1293, 1226, 1166, 1064, 771 cm−1; MS (EI) m/z 398 (M+), 344, 342, 270, 268, 258, 256, 63, 57, 56.Anal. Calcd for C19H24Cl2N2O3: C, 57.15; H, 6.06; N, 7.01; found: C, 57.20; H, 6.11; N, 6.95.

Workup

  1. waitAfter an additional 24 h
  2. washThe combined organic extracts were washed with brine
  3. dry with materialdried over Na2SO4
  4. customdecanted
  5. concentrationconcentrated
  6. customThe crude product was first purified by column chromatography (Biotage 40M, SIM) with heptane/EtOAc (1:1)

Sources & evidence

ORD record
ord-41df0dfe9ab846a9b2be6e5147f15d85
Source dataset
uspto-grants-2004_12
Patent number
US06828314B2

Reaction notes

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