Trifluoroacetic acid → HCID 178499325, compound

HRID 1046457Notes

Reaction equation

HRID 1046457 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:11]#[C:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[CH:8][C:9]=1[NH2:10])=[O:4].[O:17]1[CH2:21][CH2:20][C@H:19]([O:22][CH:23]2[CH2:28][CH2:27][C:26](=O)[CH2:25][CH2:24]2)[CH2:18]1.C(O)(C(F)(F)F)=O.C([SiH](CC)CC)C>C(Cl)Cl>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:11]#[C:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[CH:8][C:9]=1[NH:10][C@H:26]1[CH2:25][CH2:24][C@H:23]([O:22][CH:19]2[CH2:20][CH2:21][O:17][CH2:18]2)[CH2:28][CH2:27]1)=[O:4]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 24989346Methyl 3-amino-5-(3,3-dimethylbut-1-yn-1-yl)thiophene-2-carboxylateHCID 58114014HCID 58114014, compound

Product 1

HCID 178499325HCID 178499325, compoundYield 31.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 3-amino-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester (2.41 g, 10.2 mmol), 4-(tetrahydro-furan-3(S)-yloxy)-cyclohexanone (1.6 g, 8.5 mmol), TFA (2.6 mL, 34 mmol) and triethylsilane (2.7 mL, 17 mmol) in CH2Cl2 (12 mL) was stirred for 22 h at room temperature. The reaction was concentrated in vacuo and the crude oil was dissolved in toluene (50 mL) and concentrated (repeat) to give a yellow solid. The crude solid was purified by column chromatography (10-25% ethyl acetate/hexanes) to give 5-(3,3-dimethyl-but-1-ynyl)-3-[4-(tetrahydro-furan-3-yloxy)-trans-cyclohexylamino]-thiophene-2-carboxylic acid methyl ester (1.09 g, 2.69 mmol) as a single isomer.

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. dissolutionthe crude oil was dissolved in toluene (50 mL)
  3. concentrationconcentrated (repeat)
  4. customto give a yellow solid
  5. customThe crude solid was purified by column chromatography (10-25% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-a46c3e84136649a1b51367f2b3236311
Source dataset
uspto-grants-2013_10
Patent number
US08569302B2

Reaction notes

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