Hexane → HCID 86730723, compound

HRID 633850Notes

Reaction equation

HRID 633850 reaction equation
C([Li])CCC.C(OP([CH2:14][C:15]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([O:26][CH3:27])[C:23]=2[F:25])[N:18]=[CH:17][C:16]=1[Cl:28])(=O)OCC)C.[C:29]([O:33][C:34](=[O:45])[NH:35][C@@H:36]1[CH2:41][CH2:40][C@@H:39]([CH2:42][CH:43]=O)[O:38][CH2:37]1)([CH3:32])([CH3:31])[CH3:30].CCCCCC>O1CCCC1.C(OCC)(=O)C>[C:29]([O:33][C:34](=[O:45])[NH:35][C@@H:36]1[CH2:41][CH2:40][C@@H:39]([CH2:42][CH:43]=[CH:14][C:15]2[C:24]3[C:19](=[CH:20][CH:21]=[C:22]([O:26][CH3:27])[C:23]=3[F:25])[N:18]=[CH:17][C:16]=2[Cl:28])[O:38][CH2:37]1)([CH3:32])([CH3:31])[CH3:30]

Participants

7

Reactant 4

HCID 8058HexaneHCID 86730722HCID 86730722, compoundHCID 86730724HCID 86730724, compoundHCID 178418339Butyllithium

Product 1

HCID 86730723HCID 86730723, compoundYield 80.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A solution of n-butyllithium (1.6 M in n-hexane, 4.72 mL, 7.55 mmol, 1.5 eq) is added dropwise at 0° C. to a stirred solution of (3-chloro-5-fluoro-6-methoxy-quinolin-4-ylmethyl)-phosphonic acid diethyl ester (1.82 g, 5.03 mmol, 1.0 eq) in tetrahydrofuran (130 mL). After 2 hours stirring at 0° C., a solution of (3R,6S)-[6-(2-oxo-ethyl)-tetrahydro-pyran-3-yl]-carbamic acid tert-butyl ester (1.22 g, 5.03 mmol, 1.0 eq) in tetrahydrofuran (30 mL) is added dropwise within 2 minutes. After 10 minutes stirring at 0° C., the reaction mixture is quenched with water (10 mL). Then solvent is evaporated and the residue is extracted with ethyl acetate (3×150 mL) and water (100 mL). The combined organic layers are washed with brine, dried over sodium sulfate, filtered and concentrated to give a crude product that is purified by column chromatography (silica gel, eluent: n-hexane:ethyl acetate, 10:1 to 1:1, v/v) to afford (3R,6S)-{6-[3-(3-chloro-5-fluoro-6-methoxy-quinolin-4-yl)-allyl]-tetrahydro-pyran-3-yl}-carbamic acid tert-butyl ester as a light red solid (1.82 g, 80% yield).

Workup

  1. stirringAfter 10 minutes stirring at 0° C.
  2. customthe reaction mixture is quenched with water (10 mL)
  3. customThen solvent is evaporated
  4. extractionthe residue is extracted with ethyl acetate (3×150 mL) and water (100 mL)
  5. washThe combined organic layers are washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a crude product that
  10. customis purified by column chromatography (silica gel, eluent

Sources & evidence

ORD record
ord-c7205695ed624fc7972f5009c0c6c0cd
Source dataset
uspto-grants-2016_04
Patent number
US09321788B2

Reaction notes

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