Ammonium Hydroxide → (1SR,2RS)-3-amino-1-(5-fluoro-3-methyl-1H-indol-1-yl)-1-phenylpropan-2-ol

HRID 2110376Notes

Reaction equation

HRID 2110376 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C@@H:11]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C@H:12]([OH:25])[CH2:13]OS(C1C=CC(C)=CC=1)(=O)=O)[CH:6]=[C:5]2[CH3:32].[OH-].[NH4+:34]>CO>[NH2:34][CH2:13][CH:12]([OH:25])[CH:11]([N:7]1[C:8]2[C:4](=[CH:3][C:2]([F:1])=[CH:10][CH:9]=2)[C:5]([CH3:32])=[CH:6]1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

4

Reactant 2

HCID 14923Ammonium HydroxideHCID 87617828(2S,3S)-toluene-4 sulfonic acid 3-(5-fluoro-3-methyl-indol-1-yl)-2-hydroxy-3-phenyl-propyl ester

Product 1

HCID 11522248(1SR,2RS)-3-amino-1-(5-fluoro-3-methyl-1H-indol-1-yl)-1-phenylpropan-2-ol

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (2S,3S)-toluene-4 sulfonic acid 3-(5-fluoro-3-methyl-indol-1-yl)-2-hydroxy-3-phenyl-propyl ester (Intermediate in EXAMPLE 117, step 6, 0.15 g, 0.33 mmol) in methanol (10 mL) was added concentrated ammonium hydroxide (20 mL), and the reaction was stirred for 12 hours. Upon completion, the reaction was partitioned between water (25 mL) and ethyl acetate (25 mL). The organic layer was separated, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified via Biotage chromatography (FlasH40i, silica, 25% MeOH/dichloromethane) to give (1SR,2RS)-3-amino-1-(5-fluoro-3-methyl-1H-indol-1-yl)-1-phenylpropan-2-ol as a clear oil. The free base was dissolved in a minimum amount of ethanol and treated with a 4N solution of hydrochloric acid in dioxane and stirred for 1 hour s. The ethanol was removed in vacuo and the clear oil was triturated with ether/dichloromethane to give (1SR,2RS)-3-amino-1-(5-fluoro-3-methyl-1H-indol-1-yl)-1-phenylpropan-2-ol hydrochloride as a white solid. MS (ES) m/z 299.0

Workup

  1. customUpon completion, the reaction was partitioned between water (25 mL) and ethyl acetate (25 mL)
  2. customThe organic layer was separated
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified via Biotage chromatography (FlasH40i, silica, 25% MeOH/dichloromethane)

Sources & evidence

ORD record
ord-89daca5eac6f446a9683cbce46d76f76
Source dataset
uspto-grants-2009_04
Patent number
US07517899B2

Reaction notes

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