Hydrochloric Acid → HCID 67520362, compound

HRID 1923967Notes

Reaction equation

HRID 1923967 reaction equation
[OH:1][CH2:2][C@H:3]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]([F:15])([F:14])[F:13])=[CH:8][CH:7]=1.[O-:24]I(=O)(=O)=O.[Na+].CC(O)C.Cl>CC(C)=O.O.[Ru]=O>[C:19]([O:18][C:17]([NH:16][C@H:3]([CH2:4][CH2:5][C:6]1[CH:7]=[CH:8][C:9]([C:12]([F:15])([F:14])[F:13])=[CH:10][CH:11]=1)[C:2]([OH:24])=[O:1])=[O:23])([CH3:20])([CH3:22])[CH3:21]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 3776IsopropanolHCID 23667635Sodium periodateHCID 86625797tert-butyl (1R)-1-(hydroxymethyl)-3-[4-(trifluoromethyl)phenyl]propylcarbamate

Product 1

HCID 67520362HCID 67520362, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 178526987HCID 178526987, compoundCatalystHCID 180AcetoneSolvent

Procedure

To a solution of tert-butyl (1R)-1-(hydroxymethyl)-3-[4-(trifluoromethyl)phenyl]propylcarbamate IV (41.3 g; 0.124 mol) in 60% aqueous acetone was added a solid sodium (meta)periodate (266 g; 1.24 mol) followed by ruthenium(II) oxide hydrate (1.65 g; 12.4 mmol). The greenish suspension was stirred for 3 h before adding propan-2-ol (500 mL) and stirring for an additional 30 min to consume excess oxidant. The resulting suspension was filtered through Celite, and the filtrate was concentrated under reduced vacuum to give a brown oil. To the brown foam was added 1 N HCl to pH=1 which was followed by extraction with EtOAc. The organic layer was washed with brine and dried with MgSO4. The crude residue was then purified on a silica gel column (10:1 hexane:EtOAc) to obtain (2R)-2-[(tert-butoxycarbonyl)amino]-4-[4-(trifluoromethyl)phenyl]butanoic acid V (18 g; 51.8 mmol, 42% yield). 1H NMR (CDCl3) 1.46 (brs, 9H), 1.93-2.30 (m, 2H), 2.68-2.87 (m, 2H), 4.12-4.47 (m, 1H), 5.04-5.23 (m, 1H), 7.30 (d, J=8, 2H), 7.55 (d, J=8, 2H); ESIMS found for C16H20F3NO4 m/z 348.3 (M+H).

Workup

  1. stirringstirring for an additional 30 min
  2. customto consume excess oxidant
  3. filtrationThe resulting suspension was filtered through Celite
  4. concentrationthe filtrate was concentrated under reduced vacuum
  5. customto give a brown oil
  6. extractionwas followed by extraction with EtOAc
  7. washThe organic layer was washed with brine
  8. dry with materialdried with MgSO4
  9. customThe crude residue was then purified on a silica gel column (10:1 hexane:EtOAc)

Sources & evidence

ORD record
ord-b0604de82d1a4bcea2b499b779f4f4a9
Source dataset
uspto-grants-2012_05
Patent number
US08178490B2

Reaction notes

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