Acetyl chloride → HCID 25211914, compound

HRID 1514113Notes

Reaction equation

HRID 1514113 reaction equation
[F:1][C:2]([F:18])([F:17])[C:3]1[O:7][N:6]=[C:5]([C:8]2[S:12][C:11]([C:13](Cl)=[O:14])=[CH:10][CH:9]=2)[C:4]=1[CH3:16].Cl.[NH:20]1[CH2:25][CH2:24][CH2:23][C@H:22]([CH2:26][OH:27])[CH2:21]1.C(N(CC)CC)C.C(Cl)(=O)C>C1COCC1>[OH:27][CH2:26][C@H:22]1[CH2:23][CH2:24][CH2:25][N:20]([C:13]([C:11]2[S:12][C:8]([C:5]3[C:4]([CH3:16])=[C:3]([C:2]([F:18])([F:17])[F:1])[O:7][N:6]=3)=[CH:9][CH:10]=2)=[O:14])[CH2:21]1

Participants

6

Reactant 4

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 70700777(S)-Piperidin-3-ylmethanol hydrochlorideHCID 866283515-(4-Methyl-5-trifluoromethyl-isoxazol-3-yl)-thiophene-2-carbonyl chloride

Product 1

HCID 25211914HCID 25211914, compoundYield 83%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Prepared from 5-(5-Trifluoromethyl-4-methyl-isoxazol-3-yl)-thiophene-2-carbonyl chloride (74 mg, 0.25 mmol, as prepared in Example 2 Method B) and (S)-1-piperidin-3-yl-methanol, hydrochloride (76 mg, 0.5 mmol) by the method used in Example 46 for the achiral isomer. Gummy solid (70 mg, 74%). LC/MS 5.85 min, [M+1]+ 375. 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, 2 H), 1.81 (m, 1 H), 1.95 (s, 3 H), 2.00 (obs m, 1 H), 2.33 (d, J=1.3, 3 H), 3.30 (m, 2 H), 3.98 (m, 2 H), 4.10 (br d, J=11.0, 1 H), 6.10 (br d, J=6.6, 1 H), 7.43 (d, J=4.0, 1 H), 7.49 (br s, 1 H). 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. customLC/MS 5.85 min, [M+1]+ 375
  2. customevaporated
  3. customchromatographed on silica gel with EtOAc

Sources & evidence

ORD record
ord-c501030f69984e57917c9e2260b29768
Source dataset
uspto-grants-2012_07
Patent number
US08222243B2

Reaction notes

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