Imidazole → (2S,4R)-1-tert-Butyl 2-methyl 4-((tert-butyldimethylsilyl)oxy)pyrrolidine-1,2-dicarboxylate

HRID 2367022Notes

Reaction equation

HRID 2367022 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([OH:13])[CH2:10][C@H:9]1[C:14]([O:16][CH3:17])=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].N1C=CN=C1.[Si:23](Cl)([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24]>CN(C=O)C.C(OCC)(=O)C>[Si:23]([O:13][C@H:11]1[CH2:12][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[C@H:9]([C:14]([O:16][CH3:17])=[O:15])[CH2:10]1)([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24]

Participants

6

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 2734883(2S,4R)-4-Hydroxypyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester

Product 1

HCID 10618477(2S,4R)-1-tert-Butyl 2-methyl 4-((tert-butyldimethylsilyl)oxy)pyrrolidine-1,2-dicarboxylateYield 99.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Methyl (2S,4R)—N-tert-butoxycarbonyl-4-hydroxy-2-pyrrolidinecarboxylate (22.1 g, 82.6 mmol) was dissolved in dry DMF (100 mL) under nitrogen. Imidazole (16.8 g, 248 mmol) was added and the mixture cooled to 0° C. tert-Butyldimethylsilyl chloride (13.1 g, 86.7 mmol) was added in small portions and then the mixture was allowed to warm to room temperature. After stirring overnight, the mixture was diluted with 300 mL ethyl acetate and washed with water three times (500 mL, 200 mL, 200 mL). The organic extracts were washed one final time with brine and then dried over MgSO4, filtered and concentrated to give 29.5 g (99%) of desired product as a colorless oil. LC/MS (M-Boc+H)+ m/z=260.2. 1H NMR (CDCl3) δ 4.30-4.47 (m, 2H), 3.73 and 3.75 (s, 3H), 3.60 (m, 1H), 3.28-3.45 (m, 1H), 2.18 (m, 1H), 2.03 (m, 1H), 1.42 and 1.47 (s, 9H), 0.87 (s, 9H), 0.06 (s, 6H).

Workup

  1. additionwas added in small portions
  2. washwashed with water three times (500 mL, 200 mL, 200 mL)
  3. washThe organic extracts were washed one final time with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-aae2f344267a45c8bd81f0f0f09752bb
Source dataset
uspto-grants-2014_04
Patent number
US08697870B2

Reaction notes

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