Hydrochloric Acid → dimethyl(2S,5R)-5-((trimethylsilyl)ethynyl)pyrrolidine-1,2-dicarboxylate

HRID 1642652Notes

Reaction equation

HRID 1642652 reaction equation
CO[CH:3]1[N:7]([C:8]([O:10][CH3:11])=[O:9])[C@H:6]([C:12]([O:14][CH3:15])=[O:13])[CH2:5][CH2:4]1.[CH3:16][Si:17]([C:20]#[C:21][Si](C)(C)C)([CH3:19])[CH3:18].[Sn](Cl)(Cl)(Cl)Cl.[Cl-].[Al+3].[Cl-].[Cl-].C(=O)(O)[O-].[Na+].Cl>C(Cl)Cl>[CH3:16][Si:17]([C:20]#[C:21][C@H:3]1[N:7]([C:8]([O-:10])=[O:9])[C@H:6]([C:12]([O-:14])=[O:13])[CH2:5][CH2:4]1)([CH3:19])[CH3:18].[CH3:16][Si:17]([C:20]#[C:21][C@@H:3]1[N:7]([C:8]([O:10][CH3:11])=[O:9])[C@H:6]([C:12]([O:14][CH3:15])=[O:13])[CH2:5][CH2:4]1)([CH3:19])[CH3:18]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 24287Tin tetrachlorideHCID 84564Bis(trimethylsilyl)acetyleneHCID 516892Sodium BicarbonateHCID 6451240Aluminum(III) ChlorideHCID 11053097Dimethyl (2S)-5-methoxypyrrolidine-1,2-dicarboxylate

Product 2

HCID 11161884dimethyl(2S,5R)-5-((trimethylsilyl)ethynyl)pyrrolidine-1,2-dicarboxylateHCID 86592932(2S,5S)-5-((trimethylsilyl)ethynyl)pyrrolidine-1,2-dicarboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a cold −45° C. solution of dimethyl (2S)-5-methoxypyrrolidine-1,2-dicarboxylate (3.30 g, 15.20 mmol) and bistrimethylsilylacetylene (5.20 g, 30.4 mmol, 2.0 equiv) in methylene chloride (45 mL) was added a solution of tin (IV) chloride (1 Min methylene chloride, 20.0 mL, 20.0 mmol, 1.3 equiv) dropwise via syringe over 15 minutes. To the dark yellow solution was added solid aluminum chloride (2.77 g, 20.8 mmol, 1.4 equiv) in one portion. The resulting mixture was allowed to warm to room temperature and stirred at room temperature for 48 hours. The reaction mixture was carefully poured into aqueous sodium bicarbonate solution (100 mL) with ice cooling. A white precipitate forms and 1 M HCl (ca. 50 mL) was added until the solids dissolved. This mixture was extracted with ethyl acetate (2×200 mL). The combined organic layers were filtered, dried (sodium sulfate), filtered, and concentrated. The residue was chromatographed on a Biotage flash 40 M eluting with 70% hexane/30% ethyl acetate to afford (2S,5S)-5-((trimethylsilyl)ethynyl)pyrrolidine-1,2-dicarboxylate (trans compound Rf of 0.3 in 70% hexane/30% ethyl acetate) and dimethyl (2S,5R)-5-((trimethylsilyl)ethynyl)pyrrolidine-1,2-dicarboxylate (cis compound Rf of 0.2 in 70% hexane/30% ethyl acetate). Data for example 1D: MS (DCI/NH3) m/e 284 (M+H)+; The compound exists as a mixture of rotomers. 1H NMR (300 MHz, CDCl3): δ ppm 4.60 (d, 1H), 4.51 (d, 1H), 4.30 (d, 1H), 4.24 (d, 1H), 3.62 (s, 3H), 3.59 (s, 3H), 3.57 (s, 3H), 3.54 (s, 3H), 2.40-2.28 (m, 2H), 2.11-2.04 (m, 2H), 1.90-1.81 (m, 4H), 0.0 (s, 18H). Data for example 1C: MS (DCI/NH3) m/e 284 (M+H)+; 1H NMR (300 MHz, CDCl3): δ ppm 4.55-4.40 (m, 1H), 4.20-4.15 (m, 1H), 3.59 (s, 6H), 2.15-1.89 (m, 4H), 0.00 (s, 9H).

Workup

  1. dissolutiondissolved
  2. extractionThis mixture was extracted with ethyl acetate (2×200 mL)
  3. filtrationThe combined organic layers were filtered
  4. dry with materialdried (sodium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was chromatographed on a Biotage flash 40 M
  8. washeluting with 70% hexane/30% ethyl acetate

Sources & evidence

ORD record
ord-a678a5c98e874aeba6d43699b24927b2
Source dataset
uspto-grants-2012_02
Patent number
US08119664B2

Reaction notes

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