1,3-Dichloro-5,5-dimethylhydantoin → 1,1-Dimethylethyl N-[(1S)-2-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl]carbamate

HRID 1972236Notes

Reaction equation

HRID 1972236 reaction equation
[C:1](=[O:8])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])[NH2:2].[OH-].[Na+].ClN1C(C)(C)C(=O)N(Cl)C1=[O:14].[F:22][C:23]([F:33])([F:32])[C:24]1[CH:25]=[C:26]([CH:29]=[CH:30][CH:31]=1)[CH:27]=[CH2:28].S([O-])([O-])=O.[Na+].[Na+]>C(O)CC.CC[C@H]1[C@H]2C[C@H]([C@H](OC3C4C(=CC=CC=4)C(O[C@H](C4C=CN=C5C=4C=C(OC)C=C5)[C@@H]4N5C[C@H](CC)[C@@H](CC5)C4)=NN=3)C3C=CN=C4C=3C=C(OC)C=C4)N(CC2)C1>[F:22][C:23]([F:32])([F:33])[C:24]1[CH:25]=[C:26]([C@H:27]([NH:2][C:1](=[O:8])[O:3][C:4]([CH3:7])([CH3:6])[CH3:5])[CH2:28][OH:14])[CH:29]=[CH:30][CH:31]=1

Participants

8

Reactant 5

HCID 83601,3-Dichloro-5,5-dimethylhydantoinHCID 14798Sodium HydroxideHCID 24437Sodium SulfiteHCID 77922tert-Butyl carbamateHCID 5209863-(Trifluoromethyl)styrene

Product 1

HCID 708468091,1-Dimethylethyl N-[(1S)-2-hydroxy-1-[3-(trifluoromethyl)phenyl]ethyl]carbamateYield 53%

Reagents, catalysts & solvents 2

HCID 510036741-((1R)-((2R,4R,5S)-5-ethylquinuclidin-2-yl)(6-methoxyquinolin-4-yl)methoxy)-4-((1R)-((2R,4S,5R)-5-ethylquinuclidin-2-yl)(6-methoxyquinolin-4-yl)methoxy)phthalazineCatalystHCID 10311-PropanolSolvent2×

Procedure

A 500 mL round-bottomed flask is charged with tert-butyl carbamate (5.42 g, 46.0 mmol) and n-PrOH (48 mL). To this stirred solution is added freshly prepared aqueous solution of NaOH (1.84 g, 46.0 mmol in 75 mL of H2O), followed by 1,3-dichloro-5,5-dimethylhydantoin (4.54 g, 23.0 mmol). After 5 min a solution of (DHQ)2PHAL (584 mg, 0.75 mmol, 5 mol %) in n-PrOH (42 mL) is added. 3-Trifluoromethylstyrene (2.58 g, 15.0 mmol, dissolved in 60 mL of n-PrOH) is then added, followed by K2OsO2(OH)4 (221 mg, 0.6 mmol, 4 mol %). The resulting solution is stirred at rt for 2 h. The reaction mixture is then cooled in an ice-bath, and the reaction is quenched by the addition of sodium sulfite (4.41 g, 35.0 mmol) and stirred for 1 h. Evaporation to remove most of n-PrOH, the aqueous solution is extracted with ethyl acetate (4×100 mL). The combined organic phases were washed with water (50 mL), brine (50 mL), dried over anhydrous Na2SO4, and concentrated and then purified on silica gel (eluent: 0-33% ethyl acetate in hexane) to give tert-butyl (S)-1-[3-(trifluoromethyl)phenyl]-2-hydroxyethylcarbamate (2.42 g, 53%) as a colorless oil. HPLC-MS calculated for C9H11F3NO (M-Boc+H+) 206.07, found 206.10.

Workup

  1. temperatureThe reaction mixture is then cooled in an ice-bath
  2. stirringstirred for 1 h
  3. customEvaporation
  4. customto remove most of n-PrOH
  5. extractionthe aqueous solution is extracted with ethyl acetate (4×100 mL)
  6. washThe combined organic phases were washed with water (50 mL), brine (50 mL)
  7. dry with materialdried over anhydrous Na2SO4
  8. concentrationconcentrated
  9. custompurified on silica gel (eluent: 0-33% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-8dd885817e1744dbaf7656e249d0e8ef
Source dataset
uspto-grants-2013_04
Patent number
US08431607B2

Reaction notes

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