1,2-Dichloroethane → HCID 66896048, compound

HRID 1257538Notes

Reaction equation

HRID 1257538 reaction equation
Cl.[Br:2][C:3]1[CH:4]=[C:5]([CH:9]=[C:10]([C:12]2[CH2:16][C@@H:15]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=3)[O:14][N:13]=2)[CH:11]=1)[C:6]([OH:8])=O.Cl.[F:24][C:25]1[CH:26]=[CH:27][C:28]([C@H:31]([NH2:33])[CH3:32])=[N:29][CH:30]=1.C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.C(N(CC)CC)C.C(=O)(O)[O-].[Na+]>CN(C)C=O>[Br:2][C:3]1[CH:4]=[C:5]([CH:9]=[C:10]([C:12]2[CH2:16][C@@H:15]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=3)[O:14][N:13]=2)[CH:11]=1)[C:6]([NH:33][C@@H:31]([C:28]1[CH:27]=[CH:26][C:25]([F:24])=[CH:30][N:29]=1)[CH3:32])=[O:8]

Participants

8

Reactant 6

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 181649HOAtHCID 516892Sodium BicarbonateHCID 66690953(1R)-1-(5-fluoropyridin-2-yl)ethan-1-amine hydrochlorideHCID 66895359HCID 66895359, compound

Product 1

HCID 66896048HCID 66896048, compoundYield 94%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-bromo-5-[(5S)-5-(2-pyridinyl)-4,5-dihydro-3-isoxazolyl]benzoic acid hydrochloride (0.476 g, 1.24 mmol) in N,N-dimethylformamide (6 mL) were added (1R)-1-(5-fluoropyridin-2-yl)ethanamine hydrochloride (0.330 g, 1.55 mmol), EDC (416 mg, 2.17 mmol), HOAT (0.051 g, 0.372 mmol) and triethylamine (0.865 mL, 6.20 mmol). The reaction mixture was stirred at ambient temperature for 18 h. Saturated aqueous sodium bicarbonate was added. The mixture was extracted with dichloromethane (3×). The combined organic extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (50% hexanes/ethyl acetate→0% hexanes/ethyl acetate) gave the title compound (547 mg). MS 468.9 (M+1).

Workup

  1. extractionThe mixture was extracted with dichloromethane (3×)
  2. washThe combined organic extracts were washed with brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by silica gel chromatography (50% hexanes/ethyl acetate→0% hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-f06d4e334b2845758b451b38a9379bea
Source dataset
uspto-grants-2013_06
Patent number
US08461185B2

Reaction notes

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