Diisopropylethylamine → 2-{(R)-2-(tert-Butyl-dimethyl-silanyloxy)-1-[(3R,4S)-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-ethoxy}-5-chloro-pyridine

HRID 906936Notes

Reaction equation

HRID 906936 reaction equation
C([N:8]1[CH2:12][C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([Cl:20])[CH:14]=2)[C@@H:10]([C@@H:21]([O:31][C:32]2[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][N:33]=2)[CH2:22][O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[CH2:9]1)C1C=CC=CC=1.ClC(OC(Cl)C)=O.CCN(C(C)C)C(C)C>C1(C)C=CC=CC=1>[C:27]([Si:24]([CH3:26])([CH3:25])[O:23][CH2:22][C@@H:21]([C@@H:10]1[C@@H:11]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([Cl:20])[CH:14]=2)[CH2:12][NH:8][CH2:9]1)[O:31][C:32]1[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][N:33]=1)([CH3:30])([CH3:29])[CH3:28]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 5213051-Chloroethyl chloroformateHCID 671315032-[(R)-1-[(3R,4S)-1-Benzyl-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-5-chloro-pyridine

Product 1

HCID 671315312-{(R)-2-(tert-Butyl-dimethyl-silanyloxy)-1-[(3R,4S)-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-ethoxy}-5-chloro-pyridineYield 83%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 2-[(R)-1-[(3R,4S)-1-benzyl-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-5-chloro-pyridine 570 mg (0.96 mmol) dissolved in toluene (4 mL) was added 0.31 mL (2.89 mmol) of 1-chloroethyl chloroformate and 0.491 mL (2.89 mmol) of Hunig base subsequently, and the mixture was heated at 100° C. for 40 minutes, then concentrated in vaccuo. The residue was dissolved in methanol (5 mL) and stirred at room temperature over night. The mixture was concentrated in vaccuo and diluted with ethyl acetate, then washed with aq. sodium bicarbonate solution twice. The separated organic layer was dried over sodium sulfate and concentrated in vaccuo after filtration yielded 0.40 g (83%) of the title compound as a light brown oil. ES-MS m/e: 501.2 (M+H+).

Workup

  1. concentrationconcentrated in vaccuo
  2. dissolutionThe residue was dissolved in methanol (5 mL)
  3. concentrationThe mixture was concentrated in vaccuo
  4. additiondiluted with ethyl acetate
  5. washwashed with aq. sodium bicarbonate solution twice
  6. dry with materialThe separated organic layer was dried over sodium sulfate
  7. concentrationconcentrated in vaccuo
  8. filtrationafter filtration

Sources & evidence

ORD record
ord-e6c1bdb839724146a0aa7d141cce15a8
Source dataset
uspto-grants-2011_09
Patent number
US08012998B2

Reaction notes

Loading…