Imidazole → 3-(tert-Butyldimethylsilanyloxy)pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester

HRID 1014916Notes

Reaction equation

HRID 1014916 reaction equation
[CH3:1][O:2][C:3]([CH:5]1[CH:9]([OH:10])[CH2:8][CH2:7][N:6]1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[O:4].N1C=CN=C1.[Si:23](Cl)([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24]>C(Cl)Cl.Cl>[CH3:1][O:2][C:3]([CH:5]1[CH:9]([O:10][Si:23]([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24])[CH2:8][CH2:7][N:6]1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[O:4]

Participants

6

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 147292541-(tert-Butyl) 2-methyl 3-hydroxypyrrolidine-1,2-dicarboxylate

Product 1

HCID 147292563-(tert-Butyldimethylsilanyloxy)pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl esterYield 99%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution containing alcohol 38 (14.8 g, 60 mmol) in DCM (150 mL) was cooled to 0° C. To this solution was added imidazole (5.4 g, 79 mmol) followed by t-butyl-dimethylsilyl-chloride (10 g, 66 mmol) in two portions. The reaction mixture was warmed to ambient temperature over 1 h. After 5 h, the solution was diluted with 1M HCl and extracted twice with DCM. The combined organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated to afford 21.2 g (99%) of 39 as a yellow oil. 1H NMR (CDCl3, 300 MHz) δ4.38-4.34 (m, 1H), 4.18 (bs, rotomers, 0.5H), 4.04 (app d, J, =2.1 Hz, rotomers, 0.5H), 3.74 (s, 3H), 3.62-3.50 (m, 2H), 2.04-1.96 (m, 1H), 1.85-1.78 (m, 1H), 1.46 (s, minor rotomer), 1.41 (s, 9H), 0.92 (s, minor rotomer), 0.86 (s, 9H), 0.11 (s, 6H), 0.09 (s, minor rotomer) ppm.

Workup

  1. temperatureThe reaction mixture was warmed to ambient temperature over 1 h
  2. extractionextracted twice with DCM
  3. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-3c133a7ef3bc4036ad93d93e601dab17
Source dataset
uspto-grants-2011_07
Patent number
US07985735B2

Reaction notes

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