Sodium hydride → HCID 54271048, compound

HRID 1416593Notes

Reaction equation

[CH3:1][N:2]1[CH2:6][CH2:5][CH2:4][C@H:3]1[CH2:7][OH:8].[H-].[Na+].Br[C:12]1[S:13][CH:14]=[CH:15][N:16]=1>>[CH3:1][N:2]1[CH2:6][CH2:5][CH2:4][C@H:3]1[CH2:7][O:8][C:12]1[S:13][CH:14]=[CH:15][N:16]=1

Participants

Reactant 3

HCID 24758Sodium hydride

HCID 764302-Bromothiazole

HCID 643492(2S)-1-Methyl-2-pyrrolidinemethanol

Product 1

HCID 54271048HCID 54271048, compoundYield 74%

Procedure

(S)-(-)-1-Methyl-2-pyrrolidine methanol (484 mg, 4.2 mmol) was reacted with NaH ((80% dispersion in mineral oil) 0.164 g 5.46 mmol) and 2-bromothiazole (0.417 g, 4.62 mmol) according to the procedure outlined in Example 3a to afford after column chromatography eluting with (10% MeOH/CHCl3 +1% NH3) (616.2 mg, 3.1 mmol, 74% yield) of 2-(1-methyl-2-(S)-pyrrolidinylmethoxy)-thiazole. The pure base was then converted to its hydrochloride salt by treating the amine (109.4 mg, 0.552 mmol) with a saturated solution of HCl in Et2O dropwise with stirring until no more precipitate formation was observed. This afforded 21.2 mg, 0.09 mmol, 16% of the title compound. mp=99°C. [α]D20 =+2.86° (c=0.021, MeOH). MS (DCI/NH3) m/e 199 (M+H)+. 1H NMR (CD30D, 300 Mz) δ: 7.18 (d, J=4.04 Hz, 1H), 6.99 (d, J=4.04 Hz, 1H), 4.85 (dd, J=12.50, 3.31 Hz, 1H), 4.65 (dd, J=12.5, 6.62 Hz, 1H), 4.09-3.85 (m, 1H), 3.85-3.65 (m, 1H), 3.03 (br s, 3H), 2.45-2.3 (m, 1H), 2.3-1.95 (m, 3H). Analysis calculated for C9H15N2OSClΩ0.6 H2OΩ0.1Et2O: C, 44.63; H, 6.85; N, 11.07; Found: C, 44.68; H, 6.46; N, 10.68.

Workup

customto afford after column chromatography

Sources & evidence

ORD record: ord-8d360c85b39a49a28fa7af21411a7dc1
Source dataset: uspto-grants-1999_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05914328

Reaction notes

Loading…