2-(4-Bromo-2-chloro-phenyl)-1,1,1,3,3,3-hexamethyl-disilazane → 2-Butyl-2-{[3-chloro-4-(1,1,1,3,3,3-hexamethyl-disilazan-2-yl)-phenyl]-hydroxy-methyl}-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1895018Notes

Reaction equation

HRID 1895018 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]([Si:13]([CH3:16])([CH3:15])[CH3:14])[Si:9]([CH3:12])([CH3:11])[CH3:10])=[C:4]([Cl:17])[CH:3]=1.C([Li])(C)(C)C.[C:23]([O:27][C:28]([N:30]1[CH2:34][CH2:33][CH2:32][C:31]1([CH2:37][CH2:38][CH2:39][CH3:40])[CH:35]=[O:36])=[O:29])([CH3:26])([CH3:25])[CH3:24]>CCOCC>[C:23]([O:27][C:28]([N:30]1[CH2:34][CH2:33][CH2:32][C:31]1([CH2:37][CH2:38][CH2:39][CH3:40])[CH:35]([C:2]1[CH:7]=[CH:6][C:5]([N:8]([Si:13]([CH3:16])([CH3:15])[CH3:14])[Si:9]([CH3:12])([CH3:11])[CH3:10])=[C:4]([Cl:17])[CH:3]=1)[OH:36])=[O:29])([CH3:26])([CH3:25])[CH3:24]

Participants

5

Reactant 3

HCID 547539992-(4-Bromo-2-chloro-phenyl)-1,1,1,3,3,3-hexamethyl-disilazaneHCID 866208582-Butyl-2-formyl-pyrrolidine-1-carboxylic acid tert-butyl esterHCID 178418306HCID 178418306, compound

Product 1

HCID 666875552-Butyl-2-{[3-chloro-4-(1,1,1,3,3,3-hexamethyl-disilazan-2-yl)-phenyl]-hydroxy-methyl}-pyrrolidine-1-carboxylic acid tert-butyl esterYield 49.1%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

To a stirred solution of 2-(4-bromo-2-chloro-phenyl)-1,1,1,3,3,3-hexamethyl-disilazane (0.484 g, 1.38 mmol) in ether (14 mL) at −78° C. and under nitrogen was added tert-butyllithium (2.03 mL, 1.43 M solution in pentanes, 2.91 mmol) dropwise. After 90 minutes, a solution of 2-butyl-2-formyl-pyrrolidine-1-carboxylic acid tert-butyl ester (0.353 g, 1.38 mmol) in ether (3 mL) was added to the reaction mixture dropwise. After one hour, the reaction mixture was warmed to ambient temperature and stirred at ambient temperature for 30 minutes. The reaction mixture was quenched by the addition of saturated aqueous NH4Cl (10 mL) and extracted with EtOAc. The combined extracts were washed with brine, then dried (MgSO4), filtered, and concentrated in vacuo to an oil (0.75 g). Purification by chromatography (silica, 5-20% EtOAc in hexanes) gave 2-butyl-2-{[3-chloro-4-(1,1,1,3,3,3-hexamethyl-disilazan-2-yl)-phenyl]-hydroxy-methyl}-pyrrolidine-1-carboxylic acid tert-butyl ester (0.357 g, 0.678 mmol, 49%) as a colourless oil.

Workup

  1. waitAfter one hour
  2. customThe reaction mixture was quenched by the addition of saturated aqueous NH4Cl (10 mL)
  3. extractionextracted with EtOAc
  4. washThe combined extracts were washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo to an oil (0.75 g)
  8. customPurification by chromatography (silica, 5-20% EtOAc in hexanes)

Sources & evidence

ORD record
ord-2354be9ae54c47c2b196a59ce3c3f277
Source dataset
uspto-grants-2013_08
Patent number
US08513425B2

Reaction notes

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