Sodium hydride → HCID 66899159, compound

HRID 2168476Notes

Reaction equation

HRID 2168476 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 719216(S)-quinuclidin-3-amineHCID 5049666Sodium triacetoxyborohydrideHCID 86672695HCID 86672695, compound

Product 1

HCID 66899159HCID 66899159, compoundYield 72%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred suspension of (S)-(−)-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 reaction was stirred at room temperature for 2 h. Sodium triacetoxyborohydride (4.2 g, 19.6 mmol) was then 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 (S)-methyl 1-(2-(quinuclidin-3-ylamino)ethyl)-1H-indole-7-carboxylate (1.39 g, 66%) as a brown solid: 1H NMR (500 MHz, CDCl3) δ 7.79 (dd, J=4.5, 1.0 Hz, 1H), 7.69 (dd, J=4.3 Hz 1H), 7.18 (d, J=1.8 Hz, 1H), 7.10 (t, J=7.5 Hz, 1H), 6.57 (d, J=1.8 Hz, 1H), 4.51 (t, J=6.5 Hz, 2H), 3.96 (s, 3H), 3.46 (s, 1H), 3.07-3.03 (m, 1H), 2.90-2.85 (m, 1H), 2.82-2.70 (m, 5H), 2.63-2.60 (m, 1H), 2.29-2.25 (m, 1H), 1.68-1.59 (m, 3H), 1.40-1.39 (m, 1H), 1.25-1.22 (m, 1H); MS (ESI+) m/z 328 (M+H).

Workup

  1. stirringwas stirred 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-476caa1cd23c44a1951f1851e0a9ac2d
Source dataset
uspto-grants-2015_06
Patent number
US09045501B2

Reaction notes

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