Acetyl chloride → HCID 68153449, compound

HRID 1405417Notes

Reaction equation

HRID 1405417 reaction equation
[C:1](Cl)(=[O:3])[CH3:2].[CH:5]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]([N:17]2[CH2:22][CH2:21][C:20]3([NH:27][CH2:26][CH2:25][N:24]4[C:28]([C:31]([F:34])([F:33])[F:32])=[CH:29][CH:30]=[C:23]34)[CH2:19][CH2:18]2)=[O:16])=[CH:11][C:10]=1[O:35][CH3:36])([CH3:7])[CH3:6]>N1C=CC=CC=1>[CH:5]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]([N:17]2[CH2:18][CH2:19][C:20]3([N:27]([C:1](=[O:3])[CH3:2])[CH2:26][CH2:25][N:24]4[C:28]([C:31]([F:34])([F:33])[F:32])=[CH:29][CH:30]=[C:23]34)[CH2:21][CH2:22]2)=[O:16])=[CH:11][C:10]=1[O:35][CH3:36])([CH3:7])[CH3:6]

Participants

4

Reactant 2

HCID 6367Acetyl chlorideHCID 59053851HCID 59053851, compound

Product 1

HCID 68153449HCID 68153449, compoundYield 54.8%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

Acetyl chloride (158 μL, 2.22 mmol) was added drop-wise to a mixture of (4-isopropoxy-3-methoxy-phenyl)-[6-(trifluoromethyl)spiro[3,4-dihydro-2H-pyrrolo[1,2-a]pyrazine-1,4′-piperidine]-1′-yl]methanone (100 mg, 0.222 mmol) and pyridine (1 mL) at room temperature. The mixture was allowed to stir for 16 h at room temperature before it was partitioned between ethyl acetate and 1N HCl. The layers were separated and the organic layer was washed with 1N HCl, water, and then brine. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. The residue was taken up in DMF and was purified by preparatory-HPLC (10-99% ACN/water with ammonium formate modifier) to give 1-[1′-(4-isopropoxy-3-methoxy-benzoyl)-6-(trifluoromethyl)spiro[3,4-dihydropyrrolo[1,2-a]pyrazine-1,4′-piperidine]-2-yl]ethanone (60 mg, 53%) as a white solid. ESI-MS m/z calc. 493.2, found 494.7 (M+1)+; Retention time: 1.70 minutes (3 min run). 1H NMR (400 MHz, CDCl3) δ 7.06 (d, J=1.8 Hz, 1H), 7.05-6.98 (m, 1H), 6.88 (d, J=8.2 Hz, 1H), 6.55 (d, J=3.3 Hz, 1H), 6.15 (d, J=3.9 Hz, 1H), 4.57 (d, J=6.1 Hz, 1H), 4.19-4.10 (m, 2H), 3.88 (m, s, 5H), 3.79 (s, 2H), 3.70-3.52 (m, J=31.5 Hz, 2H), 3.11 (s, 2H), 2.24 (s, 3H), 1.92-1.75 (m, 2H), 1.38 (d, J=6.1 Hz, 6H).

Workup

  1. customwas partitioned between ethyl acetate and 1N HCl
  2. customThe layers were separated
  3. washthe organic layer was washed with 1N HCl, water
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customwas purified by preparatory-HPLC (10-99% ACN/water with ammonium formate modifier)

Sources & evidence

ORD record
ord-82912dda21e6476a9c09488e2324449e
Source dataset
uspto-grants-2014_12
Patent number
US08916565B2

Reaction notes

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