Methylamine → HCID 59771318, compound

HRID 2219453Notes

Reaction equation

HRID 2219453 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:11]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[CH:12]([OH:25])[CH2:13]OS(C1C=CC(C)=CC=1)(=O)=O)[CH:6]=[C:5]2[CH3:32].[CH3:33][NH2:34]>CO>[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][NH:34][CH3:33])[CH:6]=[C:5]2[CH3:32]

Participants

4

Reactant 2

HCID 6329MethylamineHCID 86600863HCID 86600863, compound

Product 1

HCID 59771318HCID 59771318, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

A solution of (2S,3S)-3-(5-fluoro-3-methyl-1H-indol-1-yl)-3-phenylpropane-1,2-diol (1.03 g, 3.4 mmol) and p-toluenesulfonyl chloride (0.78 g, 4.1 mmol) in anhydrous pyridine (11 ml) was stirred at room temperature under nitrogen for 12 hours. The reaction was poured into a 1N aqueous solution of hydrochloric acid (50 mL) and extracted with ethyl acetate (50 mL). The organics were dried over anhydrous sodium sulfate, filtered, and concentrated to give (2S,3S)-toluene-4-sulfonic acid 3-(5-fluoro-3-methyl-indol-1-yl)-2-hydroxy-3-phenyl-propyl ester. The product was used in the next step without further purification. To a solution of toluene-4-sulfonic acid 3-(5-fluoro-3-methyl-indol-1-yl)-2-hydroxy-3-phenyl-propyl ester (1.6 g, 3.4 mmol) in methanol (10 mL) was added a 2N solution of methylamine in methanol (8.6 mL, 17 mmol) and the reaction stirred for 12 hours. Upon completion, the reaction was partitioned between saturated sodium bicarbonate (50 mL) and ethyl acetate (50 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, 20% MeOH/dichloromethane) to give (1S,2R)-1-(5-fluoro-3-methyl-1H-indol-1-yl)-3-(methylamino)-1-phenylpropan-2-ol as a clear oil. The free base was dissolved in a minimum amount of ethanol and treated with a 2N ethereal solution of hydrochloric acid and stirred for 1 hour. The ethanol was removed in vacuo and the clear oil was triturated with ether/dichloromethane to give (1S,2R)-1-(5-fluoro-3-methyl-1H-indol-1-yl)-3-(methylamino)-1-phenylpropan-2-ol hydrochloride as a white solid. MS (ESI) m/z 313.

Workup

  1. customThe product was used in the next step without further purification
  2. customUpon completion, the reaction was partitioned between saturated sodium bicarbonate (50 mL) and ethyl acetate (50 mL)
  3. customThe organic layer was separated
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified via Biotage chromatography (FlasH40i, silica, 20% MeOH/dichloromethane)

Sources & evidence

ORD record
ord-e4898e3267924ae8b7fd96fa5c80db0f
Source dataset
uspto-grants-2008_08
Patent number
US07414052B2

Reaction notes

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