Trifluoroacetic acid → HCID 25254844, compound

HRID 219458Notes

Reaction equation

HRID 219458 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1)(OC(C)(C)C)=O.C(O)(C(F)(F)F)=O.BrC[CH2:24][O:25][C:26]1[C:31]([O:32][CH2:33][CH2:34][CH:35]([C:37]2[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=2)[CH3:36])=[C:30]([O:44][CH3:45])[C:29]([Cl:46])=[C:28]([CH3:47])[C:27]=1[C:48](=[O:50])[CH3:49].C([O-])([O-])=O.[Cs+].[Cs+]>C(Cl)Cl.CN(C=O)C.O>[Cl:46][C:29]1[C:28]([CH3:47])=[C:27]([C:48](=[O:50])[CH3:49])[C:26]([O:25][CH2:24][CH2:1][N:8]2[CH2:9][CH2:10][CH:11]([OH:14])[CH2:12][CH2:13]2)=[C:31]([O:32][CH2:33][CH2:34][CH:35]([C:37]2[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=2)[CH3:36])[C:30]=1[O:44][CH3:45]

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 10796Cesium carbonateHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 595835231-{2-(2-Bromo-ethoxy)-5-chloro-3-[3-(4-fluoro-phenyl)-butoxy]-4-methoxy-6-methyl-phenyl}-ethanone

Product 1

HCID 25254844HCID 25254844, compoundYield 47.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of N—BOC-4-hydroxypiperidine (42 mg, 0.21 mmol) in DCM (1 mL) was added TFA (1 mL) at room temperature and the solution was stirred for 0.1 h. The reaction mixture was concentrated under vacuum and dried on the high vacuum pump for 1 h. Example 8a (100 mg, 0.21 mmol) was added and the mixture was suspended in DMF. Cs2CO3 (123 mg, 0.38 mmol) was added in one portion and the solution was heated at 60° C. overnight. The reaction mixture was cooled to room temperature and diluted with water (20 mL) and extracted with EtOAc (3×15 mL), dried over MgSO4 and concentrated under vacuum. The crude material was purified by flash chromatography (silica-gel, MeOH/DCM 1:49) yielding the title compound (51 mg, 47%) as a clear brown oil. 1H NMR (300 MHz, CDCl3) δ 7.20-7.15 (m, 2H), 7.01-6.95 (m, 2H), 4.12 (m, 2H), 3.95 (t, J=6.6 Hz, 2H), 3.83 (s, 3H), 3.01-2.90 (m, 1H), 2.96-2.68 (m, 4H), 2.50 (s, 3H), 2.18 (s, 3H), 2.05-1.93 (m, 4H), 1.60-1.53 (m, 4H), 1.29 (d, J=6.9 Hz, 3H). MS (ES+) m/z 508 (M+H+).

Workup

  1. concentrationThe reaction mixture was concentrated under vacuum
  2. customdried on the high vacuum pump for 1 h
  3. temperatureThe reaction mixture was cooled to room temperature
  4. extractionextracted with EtOAc (3×15 mL)
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated under vacuum
  7. customThe crude material was purified by flash chromatography (silica-gel, MeOH/DCM 1:49)

Sources & evidence

ORD record
ord-4b8aeecb4843463393d8e1e47cffe318
Source dataset
uspto-grants-2012_06
Patent number
US08202513B2

Reaction notes

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