Ethyl chloroformate → (S)-2-(4-cyclohexyl-phenoxymethyl)-5-cyclopropyl-2,3-dihydro-oxazolo[3,2-a]pyrimidin-7-one

HRID 237835Notes

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.C([O:23][C:24](=O)[C:25]#[C:26][CH:27]1[CH2:29][CH2:28]1)C.C(C1CC1)#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:24](=[O:23])[CH:25]=[C:26]([CH:27]5[CH2:29][CH2:28]5)[N:15]4[CH2:14]3)=[CH:9][CH:8]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

Conditions

Temperature: 170 °C

Procedure

To a solution of (S)-5-(4-cyclohexyl-phenoxymethyl)-4,5-dihydro-oxazol-2-ylamine (0.5 g, 1.82 mmol), (see Example 28), in ethanol (5 mL) was added cyclopropyl-propynoic acid ethyl ester (0.377 g, 2.73 mmol) (prepared from ethynyl-cyclopropane and ethyl chloroformate in accordance with the procedures of G. Cai et al., Tetrahedron, 2006, 5697-5708). The reaction mixture was heated in a microwave oven at 170° C. for 30 min. The solvent was removed under vacuum, and the residue purified by flash column chromatography (silica gel, 2% 7N NH3 in MeOH/CH2Cl2) to afford 0.635 g of (S)-2-(4-cyclohexyl-phenoxymethyl)-5-cyclopropyl-2,3-dihydro-oxazolo[3,2-a]pyrimidin-7-one as a white solid. [α]D25 −13.40 (c 0.5, CHCl3)

Workup

customThe solvent was removed under vacuum
customthe residue purified by flash column chromatography (silica gel, 2% 7N NH3 in MeOH/CH2Cl2)

Sources & evidence

ORD record: ord-aecc2a065267432083b5bd97e1452303
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08642603B2

Reaction notes

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