Hydrochloric Acid → 3-(2-Bromo-1,3-thiazol-5-yl)-3-{7-[(methylsulfanyl)methyl]-1H-indol-3-yl}propan-1-ol

HRID 561530Notes

Reaction equation

HRID 561530 reaction equation
[Br:1][C:2]1[S:3][C:4]([CH:7]([C:14]2[C:22]3[C:17](=[C:18]([CH2:23][S:24][CH3:25])[CH:19]=[CH:20][CH:21]=3)[NH:16][CH:15]=2)[CH2:8][C:9](OCC)=[O:10])=[CH:5][N:6]=1.[H-].C([Al+]CC(C)C)C(C)C.C(OCC)(=O)C.Cl>O1CCCC1.CCCCCCC.O1CCCC1.O>[Br:1][C:2]1[S:3][C:4]([CH:7]([C:14]2[C:22]3[C:17](=[C:18]([CH2:23][S:24][CH3:25])[CH:19]=[CH:20][CH:21]=3)[NH:16][CH:15]=2)[CH2:8][CH2:9][OH:10])=[CH:5][N:6]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 21225700DiisobutylaluminumhydrideHCID 58392201Ethyl 3-(2-bromo-1,3-thiazol-5-yl)-3-{7-[(methylsulfanyl)methyl]-1H-indol-3-yl}propanoate

Product 1

HCID 583924633-(2-Bromo-1,3-thiazol-5-yl)-3-{7-[(methylsulfanyl)methyl]-1H-indol-3-yl}propan-1-ol

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 21263495Tetrahydrofuran heptaneSolvent

Procedure

A solution of 1.19 g (2.71 mmol) of the compound from Example 50A in 25 ml of tetrahydrofuran was added dropwise to 8.13 ml (8.13 mmol) of a 1N solution of diisobutylaluminum hydride in heptane/tetrahydrofuran and 25 ml of tetrahydrofuran at RT. The mixture was stirred at RT for 1 h, and the solution was mixed with ethyl acetate, water and 1N hydrochloric acid. The phases were separated, the aqueous phase was extracted three times with ethyl acetate, and the combined organic phases were washed with saturated aqueous sodium chloride solution. This was followed by drying over sodium sulfate, removal of the solid by filtration and removal of the solvents from the crude product in vacuo. Purification of the residue by preparative HPLC (mobile phase: acetonitrile/water gradient) resulted in 0.73 g (68% of theory) of the title compound.

Workup

  1. customThe phases were separated
  2. extractionthe aqueous phase was extracted three times with ethyl acetate
  3. washthe combined organic phases were washed with saturated aqueous sodium chloride solution
  4. dry with materialby drying over sodium sulfate, removal of the solid by filtration and removal of the solvents from the crude product in vacuo
  5. customPurification of the residue by preparative HPLC (mobile phase: acetonitrile/water gradient)

Sources & evidence

ORD record
ord-2de71e17a34f4419a8d6397abd8a0ae1
Source dataset
uspto-grants-2011_11
Patent number
US08063234B2

Reaction notes

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