2,6-Lutidine → (S)-9-(tert-butyldimethylsilyloxy)-4-chloro-7,7-dimethyl-2',3',5',6,6',7,8,9-octahydro-3H-spiro[furo[3,4-c]quinoline-1,4'-pyran]-3-one

HRID 573790Notes

Reaction equation

HRID 573790 reaction equation
[Cl:1][C:2]1[C:11]2[C:12](=[O:20])[O:13][C:14]3([CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[C:10]=2[C:9]2[C@@H:8]([OH:21])[CH2:7][C:6]([CH3:23])([CH3:22])[CH2:5][C:4]=2[N:3]=1.N1C(C)=CC=CC=1C.[C:32]([Si:36](OS(C(F)(F)F)(=O)=O)([CH3:38])[CH3:37])([CH3:35])([CH3:34])[CH3:33]>O1CCCC1>[Si:36]([O:21][C@H:8]1[CH2:7][C:6]([CH3:23])([CH3:22])[CH2:5][C:4]2[N:3]=[C:2]([Cl:1])[C:11]3[C:12](=[O:20])[O:13][C:14]4([CH2:19][CH2:18][O:17][CH2:16][CH2:15]4)[C:10]=3[C:9]1=2)([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:38])[CH3:37]

Participants

5

Reactant 3

HCID 79372,6-LutidineHCID 123564tert-Butyldimethylsilyl trifluoromethanesulphonateHCID 86662532(S)-4-chloro-9-hydroxy-7,7-dimethyl-2',3',5',6,6',7,8,9-octahydro-3H-spiro[furo[3,4-c]quinoline-1,4'-pyran]-3-one

Product 1

HCID 86662531(S)-9-(tert-butyldimethylsilyloxy)-4-chloro-7,7-dimethyl-2',3',5',6,6',7,8,9-octahydro-3H-spiro[furo[3,4-c]quinoline-1,4'-pyran]-3-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

1.69 g (S)-4-chloro-9-hydroxy-7,7-dimethyl-2′,3′,5′,6,6′,7,8,9-octahydro-3H-spiro[furo[3,4-c]quinoline-1,4′-pyran]-3-one are dissolved in 60 ml tetrahydrofurane and cooled to 0° C., 2.05 ml 2,6-lutidine and 3.71 ml trifluoromethanesulfonic acid-tert.-butyldimethylsilylester are added dropwise and the mixture is stirred for further 18 hours while warming to room temperature. Then the reaction is quenched by addition of 0.5 ml methanol. The mixture is partitioned between 0.1 M hydrochloric acid and ethylacetate. The aqueous phase is twice extracted with ethylacetate. The combined organic phases are dried with sodium sulphate and the solvents are evaporated in vacuo. The residue is chromatographed on silica gel (petrole ether/ethylacetate 100:0 to 70:30).

Workup

  1. temperaturewhile warming to room temperature
  2. customThen the reaction is quenched by addition of 0.5 ml methanol
  3. customThe mixture is partitioned between 0.1 M hydrochloric acid and ethylacetate
  4. extractionThe aqueous phase is twice extracted with ethylacetate
  5. dry with materialThe combined organic phases are dried with sodium sulphate
  6. customthe solvents are evaporated in vacuo
  7. customThe residue is chromatographed on silica gel (petrole ether/ethylacetate 100:0 to 70:30)

Sources & evidence

ORD record
ord-4503602c32a249ad94433f5b2402b24f
Source dataset
uspto-grants-2015_05
Patent number
US09029544B2

Reaction notes

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