Diisopropylethylamine → (R)-N-(1-(1H-indol-3-yl)propan-2-yl)-2-fluoro-2-methylpropan-1-amine

HRID 1749018Notes

Reaction equation

HRID 1749018 reaction equation
FC(F)(F)S(O[CH2:7][C:8]([F:11])([CH3:10])[CH3:9])(=O)=O.[NH:14]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:16]([CH2:23][C@H:24]([NH2:26])[CH3:25])=[CH:15]1.C(N(C(C)C)C(C)C)C>O1CCOCC1.CCOC(C)=O>[NH:14]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:16]([CH2:23][C@H:24]([NH:26][CH2:7][C:8]([F:11])([CH3:10])[CH3:9])[CH3:25])=[CH:15]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 448779(2R)-1-(1H-Indol-3-YL)propan-2-amineHCID 121655342-Fluoro-2-methylpropyl trifluoromethanesulfonate

Product 1

HCID 117719359(R)-N-(1-(1H-indol-3-yl)propan-2-yl)-2-fluoro-2-methylpropan-1-amineYield 91.1%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

2-Fluoro-2-methylpropyl trifluoromethanesulfonate (8.04 g, 35.87 mmol) was added to a solution of (R)-1-(1H-indol-3-yl)propan-2-amine (5.00 g, 28.70 mmol) and N-ethyl-N-isopropylpropan-2-amine (7.44 ml, 43.04 mmol) in dioxane (50 ml). The reaction was heated to 90° C. for 3 h. After cooling to room temperature, the reaction was diluted with EtOAc (200 ml) and washed with saturated. NaHCO3 solution (2×100 ml). The aqueous phase was extracted with EtOAc (150 ml), then the combined organics were dried over MgSO4 and concentrated. The crude product was purified by flash silica chromatography, elution gradient 100% EtOAc. Pure fractions were evaporated to dryness to afford (R)—N-(1-(1H-indol-3-yl)propan-2-yl)-2-fluoro-2-methylpropan-1-amine (6.49 g, 91%) as a brown oil. 1H NMR (400 MHz, CDCl3, 27° C.) δ 1.14 (3H, d), 1.31 (3H, d) 1.37 (3H, d), 1.94 (1H, s), 2.63-2.87 (3H, m), 2.92 (1H, dd), 3.07 (1H, h), 7.07 (1H, d), 7.08-7.15 (1H, m), 7.16-7.24 (1H, m), 7.37 (1H, d), 7.62 (1H, d), 8.04 (1H, s). m/z: ES+ [M+H]+ 249

Workup

  1. temperatureAfter cooling to room temperature
  2. washwashed with saturated
  3. extractionThe aqueous phase was extracted with EtOAc (150 ml)
  4. dry with materialthe combined organics were dried over MgSO4
  5. concentrationconcentrated
  6. customThe crude product was purified by flash silica chromatography, elution gradient 100% EtOAc
  7. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-b18501ed2d9e4ac79abd6ca9867e9e7e
Source dataset
uspto-grants-2015_10
Patent number
US09155727B2

Reaction notes

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