Methanol → HCID 11587638, compound

HRID 2110348Notes

Reaction equation

HRID 2110348 reaction equation
[OH:1][CH:2]([CH:7]([N:16]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:18]=[CH:17]1)[C:8]1[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=1)[C:3]([NH:5][CH3:6])=O.B.O1CCCC1.CO>O1CCCC1>[N:16]1([CH:7]([C:8]2[CH:9]=[CH:10][C:11]([O:14][CH3:15])=[CH:12][CH:13]=2)[CH:2]([OH:1])[CH2:3][NH:5][CH3:6])[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:18]=[CH:17]1

Participants

5

Reactant 3

HCID 887MethanolHCID 2723981Borane;tetrahydrofuranHCID 68905785HCID 68905785, compound

Product 1

HCID 11587638HCID 11587638, compoundYield 32%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of (2SR,3SR)-2-hydroxy-3-(1H-indol-1-yl)-3-(4-methoxyphenyl)-N-methylpropanamide (900 mg, 2.8 mmol) in anhydrous tetrahydrofuran (50 mL) at room temperature under nitrogen was added dropwise a solution of borane-tetrahydrofuran complex (1.0 M in tetrahydrofuran, 13.9 mL, 13.9 mmol) and the mixture heated to reflux for 3 hours. The reaction mixture was then cooled to 50° C., methanol (20 mL) was added, and the mixture stirred at 50° C. for 1 hour. The cooled reaction mixture was then concentrated under reduced pressure to afford a white solid. Purification by flash chromatography (silica, 15% methanol/dichloromethane) afforded 272 mg (32%) of (1SR,2RS)-1-(1H-indol-1-yl)-1-(4-methoxyphenyl)-3-(methylamino)propan-2-ol as a yellow syrup. The product was dissolved in absolute ethanol (4 mL), a solution of hydrogen chloride (4 M in 1,4-dioxane, 0.28 mL, 1.12 mmol) added, the solution stirred for 10 minutes then concentrated under reduced pressure to afford a white foam. Crystallization from 1: 1: 1 v/v absolute ethanol : diethyl ether: hexane (12 mL) at −35° C. afforded 81.3 mg (8%) of (1SR,2RS)-1-(1H-indol-1-yl)-1-(4-methoxyphenyl)-3-(methylamino)propan-2-ol hydrochloride as a hygroscopic white solid. MS (ES) m/z 311.3 ([M+H]+); HRMS: calcd for C19H22N2O2+H+, 311.17540; found (ESI, [M+H]+), 311.176.

Workup

  1. temperaturethe mixture heated
  2. temperatureto reflux for 3 hours
  3. customThe cooled reaction mixture
  4. concentrationwas then concentrated under reduced pressure
  5. customto afford a white solid
  6. customPurification by flash chromatography (silica, 15% methanol/dichloromethane)

Sources & evidence

ORD record
ord-23514017c06c48bbaa05fa31641f55f4
Source dataset
uspto-grants-2009_04
Patent number
US07517899B2

Reaction notes

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