Acetyl chloride → HCID 25211385, compound

HRID 572293Notes

Reaction equation

HRID 572293 reaction equation
Cl.[NH2:2][C@@H:3]1[CH2:8][CH2:7][CH2:6][N:5]([C:9]([C:11]2[S:12][C:13]([C:16]3[C:20]([CH3:21])=[C:19]([C:22]([F:25])([F:24])[F:23])[O:18][N:17]=3)=[CH:14][CH:15]=2)=[O:10])[CH2:4]1.C(N(CC)CC)C.[C:33](Cl)(=[O:35])[CH3:34]>C1COCC1>[CH3:21][C:20]1[C:16]([C:13]2[S:12][C:11]([C:9]([N:5]3[CH2:6][CH2:7][CH2:8][C@@H:3]([NH:2][C:33](=[O:35])[CH3:34])[CH2:4]3)=[O:10])=[CH:15][CH:14]=2)=[N:17][O:18][C:19]=1[C:22]([F:25])([F:24])[F:23]

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 131729821HCID 131729821, compound

Product 1

HCID 25211385HCID 25211385, compoundYield 83%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A suspension of ((R)-3-Amino-piperidin-1-yl)-[5-(4-methyl-5-trifluoromethyl-isoxazol-3-yl)-thiophen-2-yl]-methanone, hydrochloride (Example 27, 79 mg, 0.2 mmol) in THF (2 mL) was treated with triethylamine (70 μL, 0.5 mmol) followed by acetyl chloride (22 μL, 0.3 mmol). The reaction mixture was allowed to stir 48 hr, evaporated and chromatographed on silica gel with EtOAc then MeOH/EtOAc (10%) as eluant to afford product as a colorless solid (66 mg, 83%). 1H NMR (CDCl3) 1.65 (m, 2H), 1.81 (m, 1H), 1.95 (s, 3H), 2.00 (obs m, 1H), 2.33 (d, J=1.3, 3H), 3.30 (m, 2H), 3.98 (m, 2H), 4.10 (br d, J=11.0, 1H), 6.10 (br d, J=6.6, 1H), 7.43 (d, J=4.0, 1H), 7.49 (br s, 1H). 13C NMR 7.9, 23.5, 30.1, 46.5, 51.0 (br), 114.8, 118.7 (q, J=271), 128.3, 129.7, 131.7, 140.1, 155.2 (J=40), 157.9, 163.3, 170.3 19F NMR −63.1. LC/MS 5.72 min, [M+1]+ 402.

Workup

  1. customevaporated
  2. customchromatographed on silica gel with EtOAc

Sources & evidence

ORD record
ord-8e87883b5c1c4c2aa92da3fe5996af51
Source dataset
uspto-grants-2015_05
Patent number
US09029397B2

Reaction notes

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