Triethylamine → 3-{4-[3-(3,5-Dichloro-phenyl)-4,4,4-trifluoro-3-hydroxy-butyryl]-phenyl}-3-fluoro-azetidine-1-carboxylic acid tert-butyl ester

HRID 2277733Notes

Reaction equation

HRID 2277733 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][C:10]([C:13]2[CH:18]=[CH:17][C:16]([C:19](=[O:21])[CH3:20])=[CH:15][CH:14]=2)([F:12])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:22][C:23]1[CH:24]=[C:25]([C:30](=[O:35])[C:31]([F:34])([F:33])[F:32])[CH:26]=[C:27]([Cl:29])[CH:28]=1.C(N(CC)CC)C>CCCCCCC>[C:1]([O:5][C:6]([N:8]1[CH2:11][C:10]([C:13]2[CH:14]=[CH:15][C:16]([C:19](=[O:21])[CH2:20][C:30]([C:25]3[CH:26]=[C:27]([Cl:29])[CH:28]=[C:23]([Cl:22])[CH:24]=3)([OH:35])[C:31]([F:34])([F:33])[F:32])=[CH:17][CH:18]=2)([F:12])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 27582311-(3,5-Dichlorophenyl)-2,2,2-trifluoroethan-1-oneHCID 716803193-(4-Acetyl-phenyl)-3-fluoro-azetidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 897255463-{4-[3-(3,5-Dichloro-phenyl)-4,4,4-trifluoro-3-hydroxy-butyryl]-phenyl}-3-fluoro-azetidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8900HeptaneSolvent

Conditions

Temperature
60 °C

Procedure

In a clean and dry seal tube, to a stirred solution of 3-(4-acetyl-phenyl)-3-fluoro-azetidine-1-carboxylic acid tert-butyl ester (4 g, 13.652 mmol, 1eq.) in heptane (40 mL) was added 1-(3,5-dichlorophenyl)-2,2,2-trifluro-ethanone (6.60 gm, 27.304 mmol, 2eq.) followed by addition of triethyl amine (TEA, 3.80 ml, 27.304 mmol, 2eq.) at room temperature. Resulting reaction mixture was heated at 60° C. for 16 hours. After maximum consumption of starting material, reaction mixture was cooled to room temperature, solid precipitated out. Solid was filtered over Buchner funnel and washed with heptane (2×30 mL) and n-Pentane (70 mL) and dried under reduced pressure to get product as white solid. Yield: −5.0 g (68.31%). 1H NMR (400 MHz, CDCl3) δ: 1.47 (s, 9H), 3.68 (d, J=17.36 Hz, 1H), 3.85 (d, J=17.44 Hz, 1H), 4.17-4.24 (m, 2H), 4.39-4.47 (m, 2H), 5.69 (s, 1H), 7.33-7.35 (m, 1H), 7.48 (d, J=1.16 Hz, 2H), 7.62 (d, J=8.44 Hz, 2H), 7.98 (d, J=8.28 Hz, 2H). LC-MS (m/z): =534.0 (M−H).

Workup

  1. customIn a clean and dry
  2. customseal tube
  3. customResulting
  4. customreaction mixture
  5. customAfter maximum consumption of starting material, reaction mixture
  6. temperaturewas cooled to room temperature
  7. customsolid precipitated out
  8. filtrationSolid was filtered over Buchner funnel
  9. washwashed with heptane (2×30 mL) and n-Pentane (70 mL)
  10. customdried under reduced pressure
  11. customto get product as white solid

Sources & evidence

ORD record
ord-6c1bff4eed6944feba0e8725af124895
Source dataset
uspto-grants-2015_09
Patent number
US09133172B2

Reaction notes

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