Hydrochloric Acid → Methyl 3-amino-4-(2,4,5-trifluorophenyl)butanoate

HRID 84151Notes

Reaction equation

HRID 84151 reaction equation
[NH2:1]/[C:2](/[CH2:8][C:9]1[CH:14]=[C:13]([F:15])[C:12]([F:16])=[CH:11][C:10]=1[F:17])=[CH:3]\[C:4]([O:6][CH3:7])=[O:5].S(=O)(=O)(O)O.C([BH3-])#N.[Na+].Cl.C(=O)([O-])[O-].[Na+].[Na+]>CO.O>[NH2:1][CH:2]([CH2:8][C:9]1[CH:14]=[C:13]([F:15])[C:12]([F:16])=[CH:11][C:10]=1[F:17])[CH2:3][C:4]([O:6][CH3:7])=[O:5]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 1118Sulfuric AcidHCID 10340Sodium CarbonateHCID 5003444Sodium cyanoborohydrideHCID 49817597HCID 49817597, compound

Product 1

HCID 49820754Methyl 3-amino-4-(2,4,5-trifluorophenyl)butanoate

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

The methyl(Z)-3-amino-4-(2,4,5-trifluorophenyl)but-2-enoate (350.0 gm, 1.42 mol) (28) was charged in methanol (10.0 vol, 3.5 Ltr) at 25-30° C. and the reaction was stirred for 10-15 minutes to give a clear solution. To the clear pale yellow solution, controlled addition of sulphuric acid (70.0 ml, 0.2 vol) was done at 0 to −10° C. and the clear solution was stirred for 10-15 minutes at 0 to −10° C. After 10-15 minutes stirring at 0 to −10° C., sodium cyanoborohydride (2.0 eq, 170.0 gm) was charged in 10 lots. The clear white suspension was stirred at 0 to −10° C. for 2 hours. The methanol was distilled completely at 45-50° C. under reduced pressure to give a pale yellow residue. The pale yellow residue was further treated with a 1:1 mixture of 35% hydrochloric acid:water at 0-5° C. to give pH 2. The suspension was stirred at 0-5° C. for 10-15 minutes and the suspension was further basified by using 20% sodium carbonate to give pH 8-9. The product was extracted in ethyl acetate (2×10.0 vol, 2×3.5 Ltr). The combined ethyl acetate layers were washed with water (3×10.0 vol, 3×3.5 Ltr). The product was isolated by distillation of the ethyl acetate to give a pale yellow coloured oil.

Workup

  1. customto give a clear solution
  2. customwas done at 0 to −10° C.
  3. stirringthe clear solution was stirred for 10-15 minutes at 0 to −10° C
  4. stirringAfter 10-15 minutes stirring at 0 to −10° C.
  5. stirringThe clear white suspension was stirred at 0 to −10° C. for 2 hours
  6. distillationThe methanol was distilled completely at 45-50° C. under reduced pressure
  7. customto give a pale yellow residue
  8. stirringThe suspension was stirred at 0-5° C. for 10-15 minutes
  9. customto give pH 8-9
  10. extractionThe product was extracted in ethyl acetate (2×10.0 vol, 2×3.5 Ltr)
  11. washThe combined ethyl acetate layers were washed with water (3×10.0 vol, 3×3.5 Ltr)
  12. customThe product was isolated by distillation of the ethyl acetate
  13. customto give a pale yellow coloured oil

Sources & evidence

ORD record
ord-5af052921ce54315984c2b714a1587f5
Source dataset
uspto-grants-2014_09
Patent number
US08846916B2

Reaction notes

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