(-)-Epichlorohydrin → (S)-2-(4-Bicyclo[3.3.1]non-9-yl-phenoxymethyl)-5-fluoromethyl-2,3-dihydro-oxazolo[3,2-a]pyrimidin-7-one

HRID 237830Notes

Reaction equation

HRID 237830 reaction equation
[CH:1]12[CH:9]([C:10]3[CH:23]=[CH:22][C:13]([O:14][CH2:15][C@H:16]4[O:20][C:19]([NH2:21])=[N:18][CH2:17]4)=[CH:12][CH:11]=3)[CH:5]([CH2:6][CH2:7][CH2:8]1)[CH2:4][CH2:3][CH2:2]2.C12C(C3C=CC(O)=CC=3)C(CCC1)CCC2.C1O[C@H]1CCl.C([O:47][C:48](=O)[C:49]#[C:50][CH2:51][F:52])C>C(O)(C)(C)C>[CH:1]12[CH:9]([C:10]3[CH:23]=[CH:22][C:13]([O:14][CH2:15][C@H:16]4[O:20][C:19]5=[N:21][C:48](=[O:47])[CH:49]=[C:50]([CH2:51][F:52])[N:18]5[CH2:17]4)=[CH:12][CH:11]=3)[CH:5]([CH2:4][CH2:3][CH2:2]1)[CH2:6][CH2:7][CH2:8]2

Participants

6

Reactant 4

HCID 2734062(-)-EpichlorohydrinHCID 23234139Ethyl 4-fluorobut-2-ynoateHCID 443594624-(Bicyclo[3.3.1]nonan-9-yl)phenolHCID 68527534(S)-5-(4-bicyclo[3.3.1]non-9-yl-phenoxymethyl)-4,5-dihydro-oxazol-2-ylamine

Product 1

HCID 59252501(S)-2-(4-Bicyclo[3.3.1]non-9-yl-phenoxymethyl)-5-fluoromethyl-2,3-dihydro-oxazolo[3,2-a]pyrimidin-7-oneYield 123.5%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Procedure

To a solution of (S)-5-(4-bicyclo[3.3.1]non-9-yl-phenoxymethyl)-4,5-dihydro-oxazol-2-yl-amine (1.1 g, 3.5 mmol) (prepared from 4-bicyclo[3.3.1]non-9-yl-phenol and R-epichlorohydrin employing the procedures in Steps 1 through 2 of Example 1) in t-butanol (13 mL) was added 0.82 g (0.63 mmol) of 4-fluoro-but-2-ynoic acid ethyl ester (prepared in accordance with the procedures as described in Poulter, J Org Chem 1981, 46, 1532). The reaction mixture was refluxed for 6 hours after which it was concentrated and loaded on silica gel column and eluted with 1-6% EtOH/CH2Cl2 to afford 0.31g of the title compound. [α]D25 −26.00 (c 0.5, CHCl3).

Workup

  1. customprepared in accordance with the procedures
  2. temperatureThe reaction mixture was refluxed for 6 hours after which it
  3. concentrationwas concentrated
  4. washeluted with 1-6% EtOH/CH2Cl2

Sources & evidence

ORD record
ord-971e297b2c9442818b74139796c665e2
Source dataset
uspto-grants-2014_02
Patent number
US08642603B2

Reaction notes

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