Hydrochloric Acid → methyl 3-(S)-((3,5-bis(trifluoromethyl)phenyl)carbonylamino)-2-(R)-(4-fluorophenyl)cyclopentane-1-(R)-carboxylate

HRID 1289965Notes

Reaction equation

HRID 1289965 reaction equation
[NH2:1][C@H:2]1[CH2:6][CH2:5][C@@H:4]([C:7]([O:9][CH3:10])=[O:8])[C@@H:3]1[C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1.CCN(C(C)C)C(C)C.[F:27][C:28]([F:43])([F:42])[C:29]1[CH:30]=[C:31]([CH:35]=[C:36]([C:38]([F:41])([F:40])[F:39])[CH:37]=1)[C:32](Cl)=[O:33].Cl>C(Cl)Cl.O>[F:27][C:28]([F:42])([F:43])[C:29]1[CH:30]=[C:31]([C:32]([NH:1][C@H:2]2[CH2:6][CH2:5][C@@H:4]([C:7]([O:9][CH3:10])=[O:8])[C@@H:3]2[C:11]2[CH:12]=[CH:13][C:14]([F:17])=[CH:15][CH:16]=2)=[O:33])[CH:35]=[C:36]([C:38]([F:39])([F:40])[F:41])[CH:37]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 1018563,5-Bis(trifluoromethyl)benzoyl chlorideHCID 22885810Methyl 3-(S)-(amino)-2-(R)-(4-fluorophenyl)cyclopentane-1-(R)-carboxylate

Product 1

HCID 22885645methyl 3-(S)-((3,5-bis(trifluoromethyl)phenyl)carbonylamino)-2-(R)-(4-fluorophenyl)cyclopentane-1-(R)-carboxylateYield 49.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 100 mg of amine from Example 62 in 5 mL of methylene chloride was added 0.2 mL of DIPEA and 175 mg of 3,5-bis(trifluoromethyl)benzoyl chloride. The reaction was stirred at room temperature for 1 h and was then poured into water and 2N HCl and extracted twice with methylene chloride. The organic layers were washed with a portion of brine, combined, dried over sodium sulfate and evaporated. The residue was purified by flash chromatography eluting with 30 to 50% ethyl acetate in hexanes to obtain 100 mg of title compound. NMR (CDCl3): δ 1.8-1.9 (m, 1H), 2.05-2.2 (m, 1H), 2.2-2.4 (m, 2H), 3.08 (q, 1H), 3.42 (t, 1H), 3.67 (s, 3H), 4.65 (p, 1H), 6.80 (d, 1H), 6.99 (t, 2H), 7.22 (dd, 2H), 7.96 (s, 1H), 8.15 (s, 2H).

Workup

  1. extractionextracted twice with methylene chloride
  2. washThe organic layers were washed with a portion of brine
  3. dry with materialdried over sodium sulfate
  4. customevaporated
  5. customThe residue was purified by flash chromatography
  6. washeluting with 30 to 50% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-f6478174a400433ab66e3eb0fc41cc7c
Source dataset
uspto-grants-1998_05
Patent number
US05750549

Reaction notes

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