Trifluoroacetic anhydride → HCID 58993597, compound

HRID 391439Notes

Reaction equation

HRID 391439 reaction equation
[C:1]([C:4]1[CH:5]=[C:6]([CH2:17][O:18][CH2:19][C:20]2([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][CH2:21]2)[CH:7]=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)[CH:9]=1)(=O)[NH2:2].FC(F)(F)C(OC(=O)C(F)(F)F)=O>N1C=CC=CC=1>[C:1]([C:4]1[CH:5]=[C:6]([CH2:17][O:18][CH2:19][C:20]2([C:33]3[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=3)[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][CH2:21]2)[CH:7]=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)[CH:9]=1)#[N:2]

Participants

4

Reactant 2

HCID 9845Trifluoroacetic anhydrideHCID 58993548HCID 58993548, compound

Product 1

HCID 58993597HCID 58993597, compound

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A stirred solution of tert-butyl 4-(((5-carbamoyl-4′-fluorobiphenyl-3-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate (0.38 g, 0.72 mmol) in pyridine (6 mL) at 0° C. was treated with trifluoroacetic anhydride (1.0 mL, 7.2 mmol). The ice bath was removed and the reaction stirred at room temperature for 4 h. The reaction was cooled to 0° C. and quenched by the addition of excess methanol. The solvents were evaporated and the crude mixture dissolved in ethyl acetate and washed with 5% citric acid (2×), then water (2×), then brine (2×), dried over sodium sulfate, and concentrated. The residue was purified by column chromatography (30% ethyl acetate/hexanes) to afford 0.3 g (83%) as a white powder. 1H-NMR (CDCl3, 500 MHz) δ 7.65 (s, 1H), 7.41-7.44 (m, 3H), 7.34-7.36 (m, 4H), 7.22-7.24 (m, 2H), 7.13-7.17 (m, 2H), 4.41 (s, 2H), 3.75 (m, 2H), 3.44 (s, 2H), 2.01-3.06 (m, 2H), 2.19-2.22 (m, 2H), 1.83-1.88 (m, 2H), 1.43 (s, 9H). Mass spec.: 501.37 (MH)+.

Workup

  1. customThe ice bath was removed
  2. temperatureThe reaction was cooled to 0° C.
  3. customquenched by the addition of excess methanol
  4. customThe solvents were evaporated
  5. dissolutionthe crude mixture dissolved in ethyl acetate
  6. washwashed with 5% citric acid (2×)
  7. dry with materialwater (2×), then brine (2×), dried over sodium sulfate
  8. concentrationconcentrated
  9. customThe residue was purified by column chromatography (30% ethyl acetate/hexanes)
  10. customto afford 0.3 g (83%) as a white powder

Sources & evidence

ORD record
ord-91686781a61941dfa9c62e97d6dbef9d
Source dataset
uspto-grants-2013_02
Patent number
US08383821B2

Reaction notes

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