Water → HCID 11315058, compound

HRID 1258046Notes

Reaction equation

HRID 1258046 reaction equation
[CH2:1]([O:3][C:4]([CH:6]1[C:12]2[NH:13][C:14]3[CH2:15][CH2:16][CH2:17][CH2:18][C:19]=3[C:11]=2[CH2:10][CH2:9][N:8]([C:20](=[O:28])[C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=2)[CH2:7]1)=[O:5])[CH3:2].ClOC(C)(C)C.O>C(Cl)Cl>[CH2:1]([O:3][C:4]([C:6]1[C:12]2[NH:13][C:14]3[CH2:15][CH2:16][CH2:17][CH2:18][C:19]=3[C:11]=2[CH2:10][CH2:9][N:8]([C:20](=[O:28])[C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=2)[CH:7]=1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 962WaterHCID 521297Tert-Butyl hypochloriteHCID 11463248HCID 11463248, compound

Product 1

HCID 11315058HCID 11315058, compoundYield 10.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 3-(4-fluoro-benzoyl)-1,2,3,4,5,6,7,8,9,10-decahydro-azepino[4,5-b]indole-5-carboxylic acid ethyl ester (Example 6, 60 mg, 0.16 mmol) in DCM (2 mL) was added TEA (45 μL, 0.32 mmol) and a solution of tert-butyl hypochlorite (19.2 mL, 0.16 mmol) in DCM (1 mL) at 0° C. and the mixture was stirred for 0.5 h at 0° C. Cold water was added to quench the reaction mixture and the aqueous layer was separated and extracted with DCM. The combined organic layer was washed with water and dried over MgSO4. Evaporation of solvent gave a crude, which was purified by column chromatography on silica gel, eluting with MeOH-DCM (1:19) to give the title compound (6.5 mg) with some starting material (27 mg) recovered. 1H-NMR(CDCl3): δ 10.07 (1H, s), 7.57 (2H, m), 7.52 (1H, s), 7.10 (2H, m), 4.19 (2H, q), 4.07 (2H, t), 2.89 (2H, t), 2.62 (2H, t), 2.43 (2H, t), 1.80 (4H, m), 1.19 (3H, t). MS (ES): 383 (MH+).

Workup

  1. customto quench the reaction mixture
  2. customthe aqueous layer was separated
  3. extractionextracted with DCM
  4. washThe combined organic layer was washed with water
  5. dry with materialdried over MgSO4
  6. customEvaporation of solvent
  7. customgave a crude, which
  8. customwas purified by column chromatography on silica gel
  9. washeluting with MeOH-DCM (1:19)

Sources & evidence

ORD record
ord-568a4319145d4f7483ba0b23781d7fdb
Source dataset
uspto-grants-2013_06
Patent number
US08466143B2

Reaction notes

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