Sodium hydride → HCID 16723134, compound

HRID 555267Notes

Reaction equation

HRID 555267 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]([N:12]3[CH2:18][C:17]4([CH3:20])[CH2:19][CH:13]3[CH2:14][C:15]([CH3:22])([CH3:21])[CH2:16]4)=[O:11])=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[H-].[Na+].Br[CH:26]([CH3:32])[C:27]([O:29][CH2:30][CH3:31])=[O:28]>CN(C=O)C>[CH2:30]([O:29][C:27](=[O:28])[CH2:26][CH2:32][N:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]([N:12]3[CH2:18][C:17]4([CH3:20])[CH2:19][CH:13]3[CH2:14][C:15]([CH3:22])([CH3:21])[CH2:16]4)=[O:11])=[CH:7][CH:8]=2)[CH:3]=[CH:2]1)[CH3:31]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 79040Ethyl 2-bromopropionateHCID 11185556HCID 11185556, compound

Product 1

HCID 16723134HCID 16723134, compoundYield 37.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of (1H-indol-5-yl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)methanone (250 mg, 0.84 mmol) in dry DMF (5 mL) at room temperature under an inert atmosphere of nitrogen was added sodium hydride (30 mg, 1.26 mmol, 60% dispersion in oil), and after stirring for 30 min ethyl bromopropionate (168 mg, 0.93 mmol) was added, and the reaction mixture was stirred for 16 h at 60° C. The reaction was quenched by the addition of water (20 mL) followed by extraction with DCM (3×100 mL). The combined organic phases were dried (MgSO4), filtered and evaporated in vacuo. The resulting solid was purified by silica gel chromatography using a mixture of ethyl acetate and heptane (1:1) as eluent. Pure fractions were collected, the solvent evaporated in vacuo and dried in vacuo at 50° C. affording 125 mg (37%) of the title compound as a solid. MS-ESI m/z 397; 1H NMR (400 MHz, CDCl3) δ 0.95 (d, 3H), 1.03 (d, 3H), 1.13-1.22 (m, 7H), 1.25-1.43 (m, 2H), 1.45 (s, 1H), 1.62-1.68 (m, 1H), 1.76-1.80 (m, 1H), 2.29-2.33 (m, 1H), 2.82 (t, 2H), 3.28-3.35 (m) and 3.63 (d), 1H), 4.12-4.14 and 4.64-4.66 (m, 1H), 4.11 (q, 2H), 4.47 (t, 2H), 6.52 (d, 1H), 7.18 (d, 1H), 7.32-7.39 (m, 2H), 7.74 (d, 1H).

Workup

  1. additionwas added
  2. customThe reaction was quenched by the addition of water (20 mL)
  3. extractionfollowed by extraction with DCM (3×100 mL)
  4. dry with materialThe combined organic phases were dried (MgSO4)
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe resulting solid was purified by silica gel chromatography
  8. additiona mixture of ethyl acetate and heptane (1:1) as eluent
  9. customPure fractions were collected
  10. customthe solvent evaporated in vacuo
  11. customdried in vacuo at 50° C.

Sources & evidence

ORD record
ord-a3e5f77a08b84841a26b80528d800bec
Source dataset
uspto-grants-2011_11
Patent number
US08053431B2

Reaction notes

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