Sodium hydride → HCID 66898647, compound

HRID 2369850Notes

Reaction equation

HRID 2369850 reaction equation
[NH2:1][C@@H:2]1[CH:7]2[CH2:8][CH2:9][N:4]([CH2:5][CH2:6]2)[CH2:3]1.[H-].[Na+].O=[CH:13][CH2:14][N:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][C:22]=2[C:24]([O:26][CH3:27])=[O:25])[CH:17]=[CH:16]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.C(O)(=O)C>[N:4]12[CH2:9][CH2:8][CH:7]([CH2:6][CH2:5]1)[C@@H:2]([NH:1][CH2:13][CH2:14][N:15]1[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][C:22]=3[C:24]([O:26][CH3:27])=[O:25])[CH:17]=[CH:16]1)[CH2:3]2

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 719215(3R)-1-Azabicyclo(2.2.2)octan-3-amineHCID 5049666Sodium triacetoxyborohydrideHCID 86672695HCID 86672695, compound

Product 1

HCID 66898647HCID 66898647, compoundYield 86%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred suspension of (R)-(+)-3-aminoquinuclidine (1.4 g, 7.0 mmol) in methylene chloride (50 mL) was added sodium hydride (562 mg, 14.0 mmol) in portions and the mixture was stirred for 1 h. Acetic acid (0.6 mL) was added dropwise, followed by methyl 1-(2-oxoethyl)-1H-indole-7-carboxylate (1.3 g, 5.9 mmol) from Step B above and the mixture continued to stir at room temperature for 2 h. Sodium triacetoxyborohydride (4.2 g, 19.6 mmol) was added in one portion and stirring was continued overnight at room temperature. The solvent was removed under reduced pressure and the crude material was purified by column chromatography (silica gel, 90:10:1 methylene chloride/methanol/concentrated ammonium hydroxide) to afford (R)-methyl 1-(2-(quinuclidin-3-ylamino)ethyl)-1H-indole-7-carboxylate (1.64 g, 86%) as a brown solid: 1H NMR (500 MHz, CD3OD) δ 7.77 (d, J=4.0 Hz, 1H), 7.62 (d, J=3.8 Hz 1H), 7.30 (d, J=1.5 Hz, 1H), 7.08 (t, J=7.5 Hz, 1H), 6.58 (d, J=1.5 Hz, 1H), 4.50 (t, J=6.5 Hz, 2H), 3.96 (s, 3H), 3.35 (s, 2H), 3.00-2.97 (m, 1H), 2.85-2.58 (m, 7H), 2.21-2.17 (m, 1H), 1.70-1.56 (m, 3H), 1.44-1.42 (m, 1H), 1.27-1.25 (m, 1H); MS (ESI+) m/z 328 (M+H).

Workup

  1. stirringto stir at room temperature for 2 h
  2. stirringstirring
  3. waitwas continued overnight at room temperature
  4. customThe solvent was removed under reduced pressure
  5. customthe crude material was purified by column chromatography (silica gel, 90:10:1 methylene chloride/methanol/concentrated ammonium hydroxide)

Sources & evidence

ORD record
ord-8997c58474fa4722aa2324716c2a7ae9
Source dataset
uspto-grants-2014_04
Patent number
US08710046B2

Reaction notes

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