Acetic Acid → (2S,3R)-3-amino-1-[[3-(4-fluorophenyl)propyl](2,2,2-trifluoroethyl)amino]butan-2-ol

HRID 1592359Notes

Reaction equation

HRID 1592359 reaction equation
C([N:8](CC1C=CC=CC=1)[C@H:9]([CH3:29])[C@@H:10]([OH:28])[CH2:11][N:12]([CH2:18][CH2:19][CH2:20][C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=1)[CH2:13][C:14]([F:17])([F:16])[F:15])C1C=CC=CC=1.CC(O)=O.CCOCC>CO.[OH-].[OH-].[Pd+2]>[NH2:8][C@H:9]([CH3:29])[C@@H:10]([OH:28])[CH2:11][N:12]([CH2:18][CH2:19][CH2:20][C:21]1[CH:22]=[CH:23][C:24]([F:27])=[CH:25][CH:26]=1)[CH2:13][C:14]([F:15])([F:16])[F:17]

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 3283Diethyl EtherHCID 58997639(2S,3R)-3-(dibenzylamino)-1-[[3-(4-fluorophenyl)propyl](2,2,2-trifluoroethyl)amino]butan-2-ol

Product 1

HCID 58997676(2S,3R)-3-amino-1-[[3-(4-fluorophenyl)propyl](2,2,2-trifluoroethyl)amino]butan-2-olYield 7.9%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent2×

Procedure

Pd(OH)2 was carefully wetted down under N2 with 20 mL of MeOH and the product of Step d (3.78 g) dissolved in 50 mL of MeOH was added followed by 70 mL of HOAc. The mixture was hydrogenated for 3 days on a Parr shaker at 50 PSI. Worked up by filtering off the catalyst under N2 and vacuum through a fiberglass filter paper to obtain an oil. To the oil was added Et2O/saturated NaHCO3 (100 mL) The layers were separated. The aqueous was basified further with 1N NaOH to pH=12 then extracted 3 times with Et2O. The Et2O extracts from the 1N NaOH layer were combined, dried (Na2SO4) and stripped to give 2.46 g of and amber oil. The oil was purified by flash chromatography in 9:1 Hexanes/EtOAc to 100% EtOAc. Obtained 192 mg of an oil. MS (ESI) detects (M+H)+=323.

Workup

  1. additionwas added
  2. filtrationby filtering off the catalyst under N2
  3. filtrationvacuum through a fiberglass filter paper
  4. customto obtain an oil
  5. customwere separated
  6. extractionthen extracted 3 times with Et2O
  7. dry with materialdried (Na2SO4)
  8. customto give 2.46 g of and amber oil
  9. customThe oil was purified by flash chromatography in 9:1 Hexanes/EtOAc to 100% EtOAc

Sources & evidence

ORD record
ord-7ada2595b1394b3b96aa29c90369d8b0
Source dataset
uspto-grants-2007_11
Patent number
US07291744B2

Reaction notes

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