Ethyldi-(4-trifluormethylphenyl)phosphine → tert-butyl (3S)-3-amino-3-(5-phenylmethoxypyridin-3-yl)propanoate

HRID 526374Notes

Reaction equation

HRID 526374 reaction equation
C(P(C1C=CC(C(F)(F)F)=CC=1)C1C=CC(C(F)(F)F)=CC=1)C.[NH2:24][C:25]([C:34]1[CH:35]=[N:36][CH:37]=[C:38]([O:40][CH2:41][C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[CH:39]=1)=[CH:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28].[H][H]>FC(F)(F)CO.[Rh].C1CC=CCCC=C1.C1CC=CCCC=C1.[Cl-].[Cl-].[Rh].[Rh]>[NH2:24][C@H:25]([C:34]1[CH:35]=[N:36][CH:37]=[C:38]([O:40][CH2:41][C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[CH:39]=1)[CH2:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28]

Participants

7

Reactant 3

HCID 23212881Ethyldi-(4-trifluormethylphenyl)phosphineHCID 71259023Tert-butyl 3-amino-3-[5-(benzyloxy)pyridin-3-yl]prop-2-enoateHCID 178418361HCID 178418361, compound

Product 1

HCID 71268086tert-butyl (3S)-3-amino-3-(5-phenylmethoxypyridin-3-yl)propanoate

Reagents, catalysts & solvents 3

HCID 23948RhodiumCatalyst2×HCID 6436379Rhodium, di-mu-chlorobis((1,2,5,6-eta)-1,5-cyclooctadiene)di-CatalystHCID 64092,2,2-TrifluoroethanolSolvent3×

Procedure

To chloro(1,5-cyclooctadien)rhodium(I) dimer (29 mg, 60 μmol) and (R)-(−)-1-[(S)-2-Di-tert.-butyl-phosphino)ferrocenyl]ethyldi-(4-trifluormethylphenyl)phosphine (81 mg, 120 μmol) under an argon atmosphere was added 2,2,2-trifluoroethanol (4 mL) and the solution was stirred for 40 minutes. To tert-butyl 3-amino-3-[5-(benzyloxy)pyridin-3-yl]prop-2-enoate (1.95 g/5.97 mmol) in degassed 2,2,2-trifluoroethanol (10 mL) in a pressure vessel was added the rhodium catalyst solution and the solution was stirred for 22 hours at 50° C. under hydrogen pressure of 10 bar. The addition of an identically prepared rhodium catalyst solution in 2,2,2-trifluoroethanol (4 mL) was repeated and stirring under 10 bar hydrogen pressure at 50° C. was continued for additional 16 hours. The solution was concentrated under reduced pressure and the residue was purified by chromatography on silica gel (ethyl acetate in hexane, 12 to 100% followed by methanol in ethyl acetate 0 to 15%) to yield 1.16 g of enantiomerically enriched tert-butyl (3S)-3-amino-3-[5-(benzyloxy)pyridin-3-yl]propanoate.

Workup

  1. stirringthe solution was stirred for 22 hours at 50° C. under hydrogen pressure of 10 bar
  2. waitwas continued for additional 16 hours
  3. concentrationThe solution was concentrated under reduced pressure
  4. customthe residue was purified by chromatography on silica gel (ethyl acetate in hexane, 12 to 100% followed by methanol in ethyl acetate 0 to 15%)

Sources & evidence

ORD record
ord-2dd4b52976464750a3cca90f1ec7d647
Source dataset
uspto-grants-2016_05
Patent number
US09345793B2

Reaction notes

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