Hydrochloric Acid → 3-tert-Butyl-5-isopropyl-2-thiohydantoin

HRID 2075302Notes

Reaction equation

HRID 2075302 reaction equation
[CH2:1]1C[C@H]2N(C[C@@H]3[C@@H]4CCCCN4C[C@H]2C3)CC1.C[Li].[C:20]([N:24]1[C:28](=[O:29])[C:27](=[CH:30][CH3:31])[NH:26][C:25]1=[S:32])([CH3:23])([CH3:22])[CH3:21].Cl>C1COCC1.[NH4+].[Cl-].CCOC(C)=O>[C:20]([N:24]1[C:28](=[O:29])[CH:27]([CH:30]([CH3:1])[CH3:31])[NH:26][C:25]1=[S:32])([CH3:23])([CH3:22])[CH3:21]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 7014(+)-SparteineHCID 724744253-t-Butyl-5-ethylidenethiohydantoinHCID 178418348HCID 178418348, compound

Product 1

HCID 589574253-tert-Butyl-5-isopropyl-2-thiohydantoin

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolventHCID 25517Ammonium ChlorideSolvent

Procedure

Sparteine (0.94 g, 0.0040 mol) was dissolved in 2 mL of THF in a flask equipped with a magnetic stirrer, septum, and nitrogen pressure. The flask was immersed in a −40° bath, and a 1.6 M ethereal solution of methyllithium (2.5 mL, 0.0040 mol) was added by syringe. Then a solution of 3-t-butyl-5-ethylidenethiohydantoin (0.20 g, 0.0010 mol) in 2 mL of THF was added dropwise by syringe over 20 min. After 1 hr, HPLC analysis showed no starting material. The reaction mixture was diluted with 5 mL of saturated aqueous NH4Cl, then 4 mL of 1 M HCl, and then 10 mL of EtOAc. The layers were separated, and the organic layer was washed with 2×30 mL of 1 M HCl. The solvent was removed at aspirator pressure, and the residue was reconcentrated×3 from small amounts of dichloromethane. An HPLC trace at 270 nm revealed a purity of only 71% for the major product, although there was no major impurity. NMR (CDCl3) δ 8.5 (bs, 1H), 3.8 (m, 1H), 0.9-2.8 (m, 16H). It is notable that the methyls of the isopropyl group are magnetically nonequivalent.

Workup

  1. customequipped with a magnetic stirrer
  2. customwas immersed in a −40°
  3. customThe layers were separated
  4. washthe organic layer was washed with 2×30 mL of 1 M HCl
  5. customThe solvent was removed at aspirator pressure

Sources & evidence

ORD record
ord-d6449b47b8e74981afa19933d97f7a54
Source dataset
uspto-grants-2011_04
Patent number
US07919630B2

Reaction notes

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