Water → tert-butyl-3-(4-chloro-3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}-phenyl)propanoate

HRID 1476084Notes

Reaction equation

HRID 1476084 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([C@@H:12]([CH3:17])[C:13]([F:16])([F:15])[F:14])[C:9](Cl)=[O:10])=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.[C:27]([O:31][C:32](=[O:43])[CH2:33][CH2:34][C:35]1[CH:40]=[CH:39][C:38]([Cl:41])=[C:37]([NH2:42])[CH:36]=1)([CH3:30])([CH3:29])[CH3:28].O>C1COCC1.C(OCC)(=O)C>[C:27]([O:31][C:32](=[O:43])[CH2:33][CH2:34][C:35]1[CH:40]=[CH:39][C:38]([Cl:41])=[C:37]([NH:42][C:9](=[O:10])[C@H:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)[C@@H:12]([CH3:17])[C:13]([F:16])([F:15])[F:14])[CH:36]=1)([CH3:30])([CH3:28])[CH3:29]

Participants

7

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 58136497Tert-butyl 3-(3-amino-4-chlorophenyl)propanoateHCID 58288266(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl chloride

Product 1

HCID 58288283tert-butyl-3-(4-chloro-3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}-phenyl)propanoate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-10 °C

Procedure

18 g (70.38 mmol) of (2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl chloride were dissolved in 500 ml of THF, 18.4 ml (105.57 mmol) of N,N-diisopropylethylamine were added and the mixture was cooled to −10° C. 20.07 g (70.38 mmol) of tert-butyl-3-(3-amino-4-chlorophenyl)-propanoate, dissolved in 500 ml of THF, were then added slowly, while care was being taken not to exceed a reaction temperature of 0° C. during the addition. The mixture was then stirred for another 1 h. Water and ethyl acetate were then added to the reaction solution, the organic phase was separated off and the aqueous phase was extracted three more times with ethyl acetate. The combined organic phases were dried over sodium sulphate and concentrated on a rotary evaporator. The residue was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 20:1). This gave 30.13 g (59.74 mmol, 85% of theory) of the title compound.

Workup

  1. additionwere then added slowly, while care
  2. customa reaction temperature of 0° C.
  3. additionduring the addition
  4. customthe organic phase was separated off
  5. extractionthe aqueous phase was extracted three more times with ethyl acetate
  6. dry with materialThe combined organic phases were dried over sodium sulphate
  7. concentrationconcentrated on a rotary evaporator
  8. customThe residue was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 20:1)

Sources & evidence

ORD record
ord-b72967cfa2414d54baff44016698e4c6
Source dataset
uspto-grants-2015_04
Patent number
US09018414B2

Reaction notes

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