Reaction equation
[CH:1]1([C:7]2[CH:20]=[CH:19][C:10]([O:11][CH2:12][C@H:13]3[O:17][C:16]([NH2:18])=[N:15][CH2:14]3)=[CH:9][CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C1O[C@H]1CCl.C1(C2C=CC(O)=CC=2)CCCCC1.[CH2:39]([O:41][C:42](=O)[C:43]#[C:44][O:45]CC)[CH3:40].C(OC#C)C.ClC(OCC)=O>C(O)C>[CH:1]1([C:7]2[CH:20]=[CH:19][C:10]([O:11][CH2:12][C@H:13]3[O:17][C:16]4=[N:18][C:44](=[O:45])[CH:43]=[C:42]([O:41][CH2:39][CH3:40])[N:15]4[CH2:14]3)=[CH:9][CH:8]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1Participants
Reactant 6
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of (S)-5-(4-cyclohexyl-phenoxymethyl)-4,5-dihydro-oxazol-2-yl-amine (0.98 g, 3.58 mmol) (prepared in accordance with the procedures described in Steps 1 and 2 of Example 1 starting from R-epichlorohydrin and 4-cyclohexylphenol) in 50 ml of ethanol was added freshly prepared 3-ethoxy-propynoic acid ethyl ester (0.65 g, 4.58 mmol), prepared from 6 ml of 50% ethoxyacetylene and 3.3 ml of ethyl chloroformate (Synthesis, 1989, 123-4). The mixture was stirred for 15 min at room temperature after which it was stirred at 60-65 degrees C. for 6h. The reaction mixture was concentrated to a yellow solid, dissolved in dichloromethane and flash chromatographed on silica gel eluting with dichloromethane/ammonia/methanol to provide 0.544 g of the title compound as a white solid. [α]D25 −1.00 (c 0.5, CHCl3).
Workup
- stirringwas stirred at 60-65 degrees C
- waitfor 6h
- concentrationThe reaction mixture was concentrated to a yellow solid
- dissolutiondissolved in dichloromethane
- customflash chromatographed on silica gel eluting with dichloromethane/ammonia/methanol
Sources & evidence
- ORD record
- ord-564a3ea891ee47988b432a70fe7213e2
- Source dataset
- uspto-grants-2014_02
- Patent number
- US08642603B2
Linked notes
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