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

HRID 1749025Notes

Reaction equation

HRID 1749025 reaction equation
FC(F)(F)S(O[CH2:7][C@H:8]([CH3:11])[CH2:9][F:10])(=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@H:8]([CH3:11])[CH2:9][F:10])[CH3:25])=[CH:15]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 448779(2R)-1-(1H-Indol-3-YL)propan-2-amineHCID 117719393(S)-3-fluoro-2-methylpropyl trifluoromethanesulfonate

Product 1

HCID 117719378(S)-N-((R)-1-(1H-indol-3-yl)propan-2-yl)-3-fluoro-2-methylpropan-1-amineYield 88%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

(S)-3-Fluoro-2-methylpropyl trifluoromethanesulfonate (666 mg, 2.97 mmol) was added to a solution of (R)-1-(1H-indol-3-yl)propan-2-amine (470 mg, 2.7 mmol) and N-ethyl-N-isopropylpropan-2-amine (0.700 ml, 4.05 mmol) in 1,4-dioxane (6.05 ml). The reaction was stirred at room temperature for 1 h. The reaction mixture was diluted with EtOAc (20 ml) and washed with water (20 ml). The aqueous was extracted with EtOAc (2×20 ml), then the combined organics were dried (MgSO4) and concentrated. The crude product was purified by flash silica chromatography, elution gradient 0 to 10% methanol in DCM. Pure fractions were evaporated to dryness to afford (S)—N—((R)-1-(1H-indol-3-yl)propan-2-yl)-3-fluoro-2-methylpropan-1-amine (590 mg, 88%) as a, brown oil. 1H NMR (400 MHz, CDCl3, 30° C.) δ 0.86 (3H, dd), 1.20 (3H, d), 1.94-2.11 (1H, min), 2.64-2.74 (2H, m), 2.85-2.98 (2H, m), 3.05-3.15 (1H, m), 4.13-4.39 (2H, m), 7.09 (1H, d), 7.12 (2H, ddd), 7.20 (1H, ddd), 7.33-7.41 (1H, m), 7.56-7.65 (1H, m), 8.10 (1H, s). m/z: ES+ [M+H]+ 249

Workup

  1. washwashed with water (20 ml)
  2. extractionThe aqueous was extracted with EtOAc (2×20 ml)
  3. dry with materialthe combined organics were dried (MgSO4)
  4. concentrationconcentrated
  5. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 10% methanol in DCM
  6. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-8b532ecc11d040f187263642dee235d4
Source dataset
uspto-grants-2015_10
Patent number
US09155727B2

Reaction notes

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