Methyl iodide → 1-(N-Methyl-7-indolecarbonyl)-3-(R)-(4-(4-fluorophenyl)piperidinylmethyl)-4-(S)-(cyclopropyl)pyrrolidine

HRID 279221Notes

Reaction equation

HRID 279221 reaction equation
[CH2:1]1OCCOCCOCCOCCOCCOC1.CC([O-])(C)C.[K+].[NH:25]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][C:32]=2[C:34]([N:36]2[CH2:40][C@@H:39]([CH:41]3[CH2:43][CH2:42]3)[C@H:38]([CH2:44][N:45]3[CH2:50][CH2:49][CH:48]([C:51]4[CH:56]=[CH:55][C:54]([F:57])=[CH:53][CH:52]=4)[CH2:47][CH2:46]3)[CH2:37]2)=[O:35])[CH:27]=[CH:26]1.CI>C1COCC1>[CH3:1][N:25]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][C:32]=2[C:34]([N:36]2[CH2:40][C@@H:39]([CH:41]3[CH2:42][CH2:43]3)[C@H:38]([CH2:44][N:45]3[CH2:50][CH2:49][CH:48]([C:51]4[CH:52]=[CH:53][C:54]([F:57])=[CH:55][CH:56]=4)[CH2:47][CH2:46]3)[CH2:37]2)=[O:35])[CH:27]=[CH:26]1

Participants

6

Reactant 4

HCID 6328Methyl iodide2×HCID 2855718-Crown-6HCID 187135121-(7-Indolecarbonyl)-3-(R)-(4-(4fluorophenyl)piperidinylmethyl)-4-(S)-(cyclopropyl)pyrrolidineHCID 23665647Potassium tert-butoxide

Product 1

HCID 187135201-(N-Methyl-7-indolecarbonyl)-3-(R)-(4-(4-fluorophenyl)piperidinylmethyl)-4-(S)-(cyclopropyl)pyrrolidine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 0.015 g (0.06 mmol) of 18-crown-6 and 0.060 mL (0.06 mmol) of KOtBu (1M in THF) in 2 mL of THF was added 0.15 g (0.34 mmol) of 1-(7-indolecarbonyl)-3-(R)-(4-(4-fluorophenyl)piperidinylmethyl)-4-(S)-(cyclopropyl)pyrrolidine and the mixture was stirred for 15 min after which 0.0062 mL (0.1 mmol) methyl iodide was added. After 2 h another 0.005 mL of methyl iodide was added and the reaction mixture was stirred for 1 h. The reaction mixture was partitioned between ethyl acetate and sat'd NaHCO3 solution. The organic fraction was dried over MgSO4, filtered and the filtrate was concentrated. The residue was purified by chomatography (silica, Waters RCM 8×10 Novapak) (acetone:hexanes, 1:5) to give the title compound. 1H NMR (CD3OD) d (key peaks) 7.58 (m, 2H), 7.15-6.92 (m, 5H), 7.39 (m, 1H), 6.53 (m, 1H), 3.80 (s, 3H), 0.06 (m, 5H); Mass Spectrum (CI) m/e=460 (M+1).

Workup

  1. additionwas added
  2. customThe reaction mixture was partitioned between ethyl acetate and sat'd NaHCO3 solution
  3. dry with materialThe organic fraction was dried over MgSO4
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated
  6. customThe residue was purified by chomatography (silica, Waters RCM 8×10 Novapak) (acetone:hexanes, 1:5)

Sources & evidence

ORD record
ord-13189de332de451b86c6230ed371b1a9
Source dataset
uspto-grants-2002_03
Patent number
US06362201B1

Reaction notes

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