Triethylamine → HCID 57606122, compound

HRID 1514140Notes

Reaction equation

HRID 1514140 reaction equation
Cl.Cl.N[C@@H:4]1[CH2:9][CH:8]2[CH2:10][CH2:11][N:5]1[CH2:6][CH2:7]2.C([N:14](CC)CC)C.[F:19][C:20]([F:36])([F:35])[C:21]1[O:25][N:24]=[C:23]([C:26]2[S:30][C:29]([C:31](Cl)=[O:32])=[CH:28][CH:27]=2)[C:22]=1[CH3:34]>ClCCl>[N:5]12[CH2:11][CH2:10][CH:8]([CH2:7][CH2:6]1)[C@H:9]([NH:14][C:31]([C:29]1[S:30][C:26]([C:23]3[C:22]([CH3:34])=[C:21]([C:20]([F:36])([F:35])[F:19])[O:25][N:24]=3)=[CH:27][CH:28]=1)=[O:32])[CH2:4]2

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 67373739(s)-(-)-Aminoquinuclidine dihydrochlorideHCID 866283515-(4-Methyl-5-trifluoromethyl-isoxazol-3-yl)-thiophene-2-carbonyl chloride

Product 1

HCID 57606122HCID 57606122, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A suspension of (S)-(−)-aminoquinuclidine dihydrochloride (55 mg, 0.275 mmol) in dichloromethane (1 mL) as treated with triethylamine (53 μL, 0.55 mmol) followed by 5-(5-Trifluoromethyl-4-methyl-isoxazol-3-yl)-thiophene-2-carbonyl chloride (74 mg, 0.25 mmol) and the reaction mixture allowed to stir for 20 hr. After this time, the reaction mixture was evaporated and the residue partitioned between EtOAc (5 mL) and a 1 N HCl solution (10 mL). The aqueous portion was then basified to pH ˜10-12 with a 1N NaOH solution. The aqueous portion was then extracted with EtOAc (10 mL) which was then washed with a brine solution (10 mL), dried over MgSO4, filtered, and evaporated in vacuo to afford product as a colorless solid (38 mg, 40%). 1H NMR (CDCl3) 1.50-1.62 (m, 1H), 1.70-1.88 (m, 3H), 2.08-2.12 (m, 2H), 2.37 (d, J=1.3, 3H), 2.72-3.10 (m, 5H), 3.44 (ddd, J=14.0, 9.7, 2.2, 1H), 4.14-4.22 (m, 1H), 6.56 (br d, J=7.0, 1H), 7.49 (d, J=4.0, 1H), 7.56 (d, J=4.0, 1H). 19F NMR −63.13. LC/MS 4.63 min, [M+1]+ 386.

Workup

  1. customAfter this time, the reaction mixture was evaporated
  2. customthe residue partitioned between EtOAc (5 mL)
  3. extractionThe aqueous portion was then extracted with EtOAc (10 mL) which
  4. washwas then washed with a brine solution (10 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated in vacuo

Sources & evidence

ORD record
ord-5eef000263b04b6a92f7159cdacd610f
Source dataset
uspto-grants-2012_07
Patent number
US08222243B2

Reaction notes

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