2,6-Lutidine → HCID 86650529, compound

HRID 403449Notes

Reaction equation

HRID 403449 reaction equation
[CH2:1]([C@H:8]1[CH2:13][CH2:12][O:11][C:10](=[O:14])[N:9]1[C:15](=[O:30])[C@@H:16]([C@@H:21]([C:23]1[CH:24]=[N:25][C:26]([Cl:29])=[CH:27][CH:28]=1)[OH:22])[CH2:17][CH2:18][C:19]#[CH:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C(C)=CC=CC=1C.FC(F)(F)S(O[Si:45]([C:48]([CH3:51])([CH3:50])[CH3:49])([CH3:47])[CH3:46])(=O)=O>ClCCl>[CH2:1]([C@H:8]1[CH2:13][CH2:12][O:11][C:10](=[O:14])[N:9]1[C:15](=[O:30])[C@@H:16]([C@H:21]([O:22][Si:45]([C:48]([CH3:51])([CH3:50])[CH3:49])([CH3:47])[CH3:46])[C:23]1[CH:24]=[N:25][C:26]([Cl:29])=[CH:27][CH:28]=1)[CH2:17][CH2:18][C:19]#[CH:20])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 79372,6-LutidineHCID 123564tert-Butyldimethylsilyl trifluoromethanesulphonateHCID 86650528HCID 86650528, compound

Product 1

HCID 86650529HCID 86650529, compoundYield 97%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 29.7 g (71.9 mmol) of (4S)-4-benzyl-3-{(2R)-2-[(S)-(6-chloropyridin-3-yl)(hydroxy)methyl]hex-5-ynoyl}-1,3-oxazinan-2-one from Step B above and 15.0 mL (126 mmol) of 2,6-lutidine in 300 mL of anhydrous dichloromethane at 0° C. under an atmosphere of nitrogen was added 22 mL (94 mmol) of tert-butyldimethylsilyl trifluoromethanesulfonate at a rate slow enough to keep the internal temperature below 3° C. The reaction mixture was stirred for 16 h at 0° C. then evaporated in vacuo to remove all volatiles. The residue was diluted with 400 mL of water and extracted with diethyl ether (3×300 mL). The combined organics were washed sequentially with a 0.5 M aqueous hydrochloric acid solution (100 mL), water (100 mL) brine (100 mL) then dried over magnesium sulfate. After filtration and evaporation in vacuo the residue was purified by silica gel chromatography eluting with a 5-8% ethyl acetate in hexanes gradient to afford the title compound as a colorless foam (37 g, 97%). LC-MS: m/z (ES) 527.3 (MH)+.

Workup

  1. customthe internal temperature below 3° C
  2. customthen evaporated in vacuo
  3. customto remove all volatiles
  4. additionThe residue was diluted with 400 mL of water
  5. extractionextracted with diethyl ether (3×300 mL)
  6. washThe combined organics were washed sequentially with a 0.5 M aqueous hydrochloric acid solution (100 mL), water (100 mL) brine (100 mL)
  7. dry with materialthen dried over magnesium sulfate
  8. filtrationAfter filtration and evaporation in vacuo the residue
  9. customwas purified by silica gel chromatography
  10. washeluting with a 5-8% ethyl acetate in hexanes gradient

Sources & evidence

ORD record
ord-5a8e94f75c944e9cb063fd1911d9a4e9
Source dataset
uspto-grants-2014_06
Patent number
US08748433B2

Reaction notes

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