Water → HCID 57995592, compound

HRID 385369Notes

Reaction equation

HRID 385369 reaction equation
[CH3:1][O:2][C:3](=[O:23])[CH:4]([C:10]1[CH:15]=[CH:14][C:13]([NH2:16])=[C:12]([O:17][CH2:18][C:19]([F:22])([F:21])[F:20])[CH:11]=1)[CH2:5][CH:6]1[CH2:9][CH2:8][CH2:7]1.[Br:24]N1C(=O)CCC1=O.O.C(Cl)Cl>C(Cl)(Cl)Cl>[CH3:1][O:2][C:3](=[O:23])[CH:4]([C:10]1[CH:11]=[C:12]([O:17][CH2:18][C:19]([F:22])([F:21])[F:20])[C:13]([NH2:16])=[C:14]([Br:24])[CH:15]=1)[CH2:5][CH:6]1[CH2:7][CH2:8][CH2:9]1

Participants

6

Reactant 4

HCID 962WaterHCID 6344DichloromethaneHCID 67184N-bromobutanimideHCID 579956482-[4-Amino-3-(2,2,2-trifluoro-ethoxy)-phenyl]-3-cyclobutyl-propionic acid Methyl Ester

Product 1

HCID 57995592HCID 57995592, compoundYield 106.6%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of the 2-[4-amino-3-(2,2,2-trifluoro-ethoxy)-phenyl]-3-cyclobutyl-propionic acid methyl ester (12.3 g, 31.8 mmol) in chloroform (150 mL) was added N-bromosuccinimide (7 g, 39.3 mmol). The reaction mixture was stirred at 25° C. for 16 h and a mixture of water and methylene chloride (100 mL/100 mL) was added. The reaction mixture was extracted with methylene chloride (2×50 mL) and the organic phases were separated. The combined organic phases were dried over MgSO4 and evaporated to give a crude yellow oil, which was purified by a short silica gel column chromatography eluting with heptane-EtOAc (4:1) to give the product (13.9 g, 94%) as a yellowish oil. 1H NMR (300 MHz, CDCl3/TMS): δ 7.06 (d, J=1.1 Hz, 1H), 6.70 (d, J=1.2 Hz, 1H), 4.37 (q, J=8.0 Hz, 2H), 4.21 (br s, 2H), 3.64 (s, 3H), 3.31 (t, J=7.7 Hz, 1H), 2.20-1.89 (m, 4H), 1.81-1.75 (m, 3H), 1.67-1.51 (m, 2H). 13C NMR (75 MHz, CDCl3/TMS): δ 174.2, 144.6, 134.4, 128.9, 125.7, 123.0 (d, 1JCF=277.6 Hz), 110.9, 108.7, 66.5 (q, 1JCF=36.0 Hz), 52.0, 48.6, 40.7, 33.9, 28.3, 28.0, 18.5.

Workup

  1. additionwas added
  2. extractionThe reaction mixture was extracted with methylene chloride (2×50 mL)
  3. customthe organic phases were separated
  4. dry with materialThe combined organic phases were dried over MgSO4
  5. customevaporated
  6. customto give a crude yellow oil, which
  7. customwas purified by a short silica gel column chromatography
  8. washeluting with heptane-EtOAc (4:1)

Sources & evidence

ORD record
ord-267deb3e07a24d6b913badb0eb4f1a6d
Source dataset
uspto-grants-2013_02
Patent number
US08367863B2

Reaction notes

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