Quinine → (2S,3R)-2-(tert-butoxycarbonylamino)-3-hydroxy-3-(4-(trifluoromethyl)phenyl)propanoic acid

HRID 1425923Notes

Reaction equation

HRID 1425923 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH:13]([OH:24])[C:14]1[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=1)[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].COC1C=CC2N=CC=C([C@@H](O)[C@H]3N4C[C@H](C=C)[C@@H](CC4)C3)C=2C=1.CC1(C)O[C@]2(OC[C@@H]3OC(C)(C)O[C@@H]3C2=O)CO1>CCOCC>[C:1]([O:5][C:6]([NH:8][C@@H:9]([C@H:13]([OH:24])[C:14]1[CH:15]=[CH:16][C:17]([C:20]([F:22])([F:23])[F:21])=[CH:18][CH:19]=1)[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 3034034QuinineHCID 11391247L-enantiomerHCID 68281361(R)-2-(tert-butoxycarbonylamino)-3-hydroxy-3-(4-(trifluoromethyl)phenyl)propanoic acid

Product 1

HCID 69283154(2S,3R)-2-(tert-butoxycarbonylamino)-3-hydroxy-3-(4-(trifluoromethyl)phenyl)propanoic acidYield 68%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

To a solution of (R)-2-(tert-butoxycarbonylamino)-3-hydroxy-3-(4-(trifluoromethyl)phenyl)propanoic acid (LXXVIII) (35 g, 100 mmol) in Et2O (600 mL) was added quinine (34 g, 100 mmol) in portions. The reaction was stirred at room temperature for 30 min at which time the white precipitate (L-enantiomer salt) was filtered and washed with Et2O. The solid was taken up in EtOAc/aqueous KHSO4. The organic layer was washed with aqueous KHSO4, brine and dried over MgSO4. The solvent was removed in vacuo to give optically pure (Marfey test) (2S,3R)-2-(tert-butoxycarbonylamino)-3-hydroxy-3-(4-(trifluoromethyl)phenyl)propanoic acid (LXXIX) (12 g, 34 mmol, 68% yield). 1H NMR (DMSO-d6) δ ppm 1.33 (s, 9H), 4.09 (brs, 1H), 5.13 (brs, 1H), 5.56 (brs, 1H), 7.47 (d, J=8 Hz, 2H), 7.56 (d, J=8 Hz, 2H); 19F NMR (DMSO-d6) δ ppm −60.15; ESIMS found for C15H18F3NO5 m/z 348 (M−H)

Workup

  1. filtrationwas filtered
  2. washwashed with Et2O
  3. washThe organic layer was washed with aqueous KHSO4, brine
  4. dry with materialdried over MgSO4
  5. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-569652b1339c4813b5c3ced59a6729c0
Source dataset
uspto-grants-2015_01
Patent number
US08933018B2

Reaction notes

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