Thionyl Chloride → methyl (3R,4R)-1-tert-butyloxycarbonyl-4-[3-(3-fluoro-6-methoxyquinolin-4-yl)-3-oxopropyl]piperidine-3-carboxylate

HRID 1767093Notes

Reaction equation

HRID 1767093 reaction equation
S(Cl)(Cl)=O.[C:5]([O:9][C:10]([N:12]1[CH2:17][CH2:16][C@@H:15]([CH2:18][CH2:19][C:20]([C:22]2[C:31]3[C:26](=[CH:27][CH:28]=[C:29]([O:32][CH3:33])[CH:30]=3)[N:25]=[CH:24][C:23]=2[F:34])=[O:21])[C@@H:14]([C:35]([OH:37])=[O:36])[CH2:13]1)=[O:11])([CH3:8])([CH3:7])[CH3:6].[CH:38](N(CC)C(C)C)(C)C>ClCCl.CO>[C:5]([O:9][C:10]([N:12]1[CH2:17][CH2:16][C@@H:15]([CH2:18][CH2:19][C:20]([C:22]2[C:31]3[C:26](=[CH:27][CH:28]=[C:29]([O:32][CH3:33])[CH:30]=3)[N:25]=[CH:24][C:23]=2[F:34])=[O:21])[C@@H:14]([C:35]([O:37][CH3:38])=[O:36])[CH2:13]1)=[O:11])([CH3:8])([CH3:6])[CH3:7]

Participants

6

Reactant 3

HCID 24386Thionyl ChlorideHCID 81531DiisopropylethylamineHCID 69345870(3R,4R)-1-tertbutyloxycarbonyl-4-[3-(3-fluoro-6-methoxyquinolin-4-yl)-3-oxopropyl]piperidine-3-carboxylic acid

Product 1

HCID 86592160methyl (3R,4R)-1-tert-butyloxycarbonyl-4-[3-(3-fluoro-6-methoxyquinolin-4-yl)-3-oxopropyl]piperidine-3-carboxylate

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
20 °C

Procedure

1.58 cm3 of a thionyl chloride solution are added, at a temperature in the region of 20° C., under an argon atmosphere, to 3.33 g (7.23 mmol) of (3R,4R)-1-tertbutyloxycarbonyl-4-[3-(3-fluoro-6-methoxyquinolin-4-yl)-3-oxopropyl]piperidine-3-carboxylic acid in solution in 150 cm3 of dichloromethane. After stirring for 1 hour at a temperature in the region of 20° C., the reaction mixture is poured over a solution of 10.55 cm3 of N,N-diisopropylethylamine in 150 cm3 of methanol. After stirring for 16 hours at a temperature in the region of 20° C., the reaction mixture is concentrated to dryness under reduced pressure (2.7 kPa). The residue is taken up with 150 cm3 of CH2Cl2, and washed with 3 times 50 cm3 of water and then 50 cm3 of a saturated aqueous sodium chloride solution. The organic phase is dried over anhydrous magnesium sulfate, filtered, and concentrated to dryness under reduced pressure (2.7 kPa) to give 4 g of methyl (3R,4R)-1-tert-butyloxycarbonyl-4-[3-(3-fluoro-6-methoxyquinolin-4-yl)-3-oxopropyl]piperidine-3-carboxylate in the form of an orange oil.

Workup

  1. stirringAfter stirring for 16 hours at a temperature in the region of 20° C.
  2. concentrationthe reaction mixture is concentrated to dryness under reduced pressure (2.7 kPa)
  3. washwashed with 3 times 50 cm3 of water
  4. dry with materialThe organic phase is dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)

Sources & evidence

ORD record
ord-7f1868af0b1f4eb8a520efdf3908fbcf
Source dataset
uspto-grants-2007_06
Patent number
US07232834B2

Reaction notes

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