Diisopropylamine → tert-butyl 1-oxo-2-((1-tosyl-1H-indol-3-yl)methyl)-2,9-diazaspiro[5.5]undecane-9-carboxylate

HRID 41572

Reaction equation

HRID 41572 reaction equation
C(NC(C)C)(C)C.[O:8]=[C:9]1[C:14]2([CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]2)[CH2:13][CH2:12][CH2:11][NH:10]1.Br[CH2:28][C:29]1[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[N:31]([S:38]([C:41]2[CH:47]=[CH:46][C:44]([CH3:45])=[CH:43][CH:42]=2)(=[O:40])=[O:39])[CH:30]=1>C1COCC1>[O:8]=[C:9]1[C:14]2([CH2:15][CH2:16][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:18][CH2:19]2)[CH2:13][CH2:12][CH2:11][N:10]1[CH2:28][C:29]1[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[N:31]([S:38]([C:41]2[CH:42]=[CH:43][C:44]([CH3:45])=[CH:46][CH:47]=2)(=[O:40])=[O:39])[CH:30]=1

Participants

5

Reactant 3

HCID 7912DiisopropylamineHCID 112685123-(Bromomethyl)-1-tosyl-1H-indoleHCID 49760149tert-Butyl 1-oxo-2,9-diazaspiro[5.5]undecane-9-carboxylate

Product 1

HCID 67253831tert-butyl 1-oxo-2-((1-tosyl-1H-indol-3-yl)methyl)-2,9-diazaspiro[5.5]undecane-9-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To a solution of diisopropylamine (1.238 mL, 8.60 mmol) in THF (40 mL) n-butyllithium (6.01 mL, 9.61 mmol) was added at 0° C. and the mixture was stirred for 30 min at 0° C. Then a solution of tert-butyl 1-oxo-2,9-diazaspiro[5.5]undecane-9-carboxylate [1198284-94-4] (2.57 g, 9.28 mmol) in THF (10 mL) was added within 3 min and the mixture was stirred for 30 min at 0° C. 3-(bromomethyl)-1-tosyl-1H-indole [58550-81-5] (3.2 g, 8.43 mmol) in THF (10 mL) was dropped to the reaction mixture within 15 min. The mixture was stirred at 0° C. for 1 h and allowed to warm to room temperature overnight. The reaction mixture was quenched with ice-cold water and extracted with TBME (2×150 mL). The combined organic layers were washed with 5% aqueous citric acid and brine, dried over anhydrous Na2SO4, filtered and concentrated (5.3 g, 100%). [1H NMR (400 MHz, DMSO-d8) ♀ ppm 7.88 (d, J=8.28 Hz, 1H), 7.81 (d, J=8.28 Hz, 2H), 7.74 (s, 1H), 7.55 (d, J=7.78 Hz, 1H), 7.36 (d, J=8.03 Hz, 2H), 7.32 (t, J=7.91 Hz, 1H), 7.25-7.21 (m, 1H), 4.58 (s, 2H), 3.75-3.63 (m, 2H), 3.09 (t, J=5.77 Hz, 2H), 2.99 (br. s., 2H), 2.30 (s, 3H), 1.90-1.80 (m, 2H), 1.72-1.57 (m, 4H), 1.39 (s, 9H), 1.36-1.28 (m, 2H); LCMS RtA=1.37 min, [M+H]+=552.3].

Workup

  1. stirringthe mixture was stirred for 30 min at 0° C
  2. stirringThe mixture was stirred at 0° C. for 1 h
  3. temperatureto warm to room temperature overnight
  4. customThe reaction mixture was quenched with ice-cold water
  5. extractionextracted with TBME (2×150 mL)
  6. washThe combined organic layers were washed with 5% aqueous citric acid and brine
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated (5.3 g, 100%)
  10. custom[1H NMR (400 MHz, DMSO-d8) ♀ ppm 7.88 (d, J=8.28 Hz, 1H), 7.81 (d, J=8.28 Hz, 2H), 7.74 (s, 1H), 7.55 (d, J=7.78 Hz, 1H), 7.36 (d, J=8.03 Hz, 2H), 7.32 (t, J=7.91 Hz, 1H), 7.25-7.21 (m, 1H), 4.58 (s, 2H), 3.75-3.63 (m, 2H), 3.09 (t, J=5.77 Hz, 2H), 2.99 (br. s., 2H), 2.30 (s, 3H), 1.90-1.80 (m, 2H), 1.72-1.57 (m, 4H), 1.39 (s, 9H), 1.36-1.28 (m, 2H); LCMS RtA=1.37 min, [M+H]+=552.3]

Sources & evidence

ORD record
ord-04a18bd689c04055bf805fc0d78dd456
Source dataset
uspto-grants-2013_09
Patent number
US08530648B2

Linked notes

Loading…