Trifluoroacetic acid → 4-[4-(4-Fluorophenyl)-1-piperidin-4-yl-1H-imidazol-5-yl]pyrimidine

HRID 1896653Notes

Reaction equation

HRID 1896653 reaction equation
C(O)(C(F)(F)F)=O.[F:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[N:16]=[CH:17][N:18]([CH:26]3[CH2:31][CH2:30][N:29](C(OC(C)(C)C)=O)[CH2:28][CH2:27]3)[C:19]=2[C:20]2[CH:25]=[CH:24][N:23]=[CH:22][N:21]=2)=[CH:11][CH:10]=1.[OH-].[Na+]>ClCCl>[F:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[N:16]=[CH:17][N:18]([CH:26]3[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]3)[C:19]=2[C:20]2[CH:25]=[CH:24][N:23]=[CH:22][N:21]=2)=[CH:13][CH:14]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 58235130tert-butyl 4-[4-(4-fluorophenyl)-5-pyrimidin-4-yl-1H-imidazol-1-yl]piperidine-1-carboxylate

Product 1

HCID 574617184-[4-(4-Fluorophenyl)-1-piperidin-4-yl-1H-imidazol-5-yl]pyrimidine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (242 mL) was added to a solution of tert-butyl 4-[4-(4-fluorophenyl)-5-pyrimidin-4-yl-1H-imidazol-1-yl]piperidine-1-carboxylate (C14) (30.70 g, 72.49 mmol) in dichloromethane (242 mL). After 18 hours, the reaction was treated with aqueous sodium hydroxide solution (2 N) until the pH of the mixture reached 12.0. {Caution: potential exotherm!} The aqueous layer was extracted with dichloromethane (2×500 mL), and the combined organic layers were concentrated in vacuo to provide the product as a yellowish solid. Yield: 23.90 g, 73.91 mmol, quantitative. 1H NMR (400 MHz, CDCl3) δ 1.82-1.92 (m, 2H), 2.14 (br d, J=12 Hz, 2H), 2.71 (ddd, J=12.3, 12.3, 2.2 Hz, 2H), 3.22 (br d, J=12 Hz, 2H), 4.82 (tt, J=12.0, 3.9 Hz, 1H), 7.03 (dd, J=8.8, 8.8 Hz, 2H), 7.16 (dd, J=5.3, 1.4 Hz, 1H), 7.41 (dd, J=8.9, 5.4 Hz, 2H), 7.83 (s, 1H), 8.57 (d, J=5.3 Hz, 1H), 9.30 (d, J=1.4 Hz, 1H).

Workup

  1. extractionThe aqueous layer was extracted with dichloromethane (2×500 mL)
  2. concentrationthe combined organic layers were concentrated in vacuo

Sources & evidence

ORD record
ord-9632db3ce3474e3084534943d158b5bf
Source dataset
uspto-grants-2013_08
Patent number
US08518944B2

Reaction notes

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