Hexane → HCID 86730725, compound

HRID 633851Notes

Reaction equation

HRID 633851 reaction equation
CC(C)([O-])C.[K+].[C:7]([O:11][C:12](=[O:39])[NH:13][CH:14]1[CH2:19][CH2:18][CH:17]([CH2:20][CH:21]([OH:38])[CH:22]([C:24]2[C:33]3[C:28](=[CH:29][CH:30]=[C:31]([O:35][CH3:36])[C:32]=3[F:34])[N:27]=[CH:26][C:25]=2Cl)[OH:23])[O:16][CH2:15]1)([CH3:10])([CH3:9])[CH3:8].C(P(C(C)(C)C)C1C=CC2C(=CC=CC=2)C=1C1C2C(=CC=CC=2)C=CC=1)(C)(C)C.CCCCCC>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C>[C:7]([O:11][C:12](=[O:39])[NH:13][C@@H:14]1[CH2:19][CH2:18][C@@H:17]([CH2:20][CH:21]2[O:38][C:25]3[CH:26]=[N:27][C:28]4[CH:29]=[CH:30][C:31]([O:35][CH3:36])=[C:32]([F:34])[C:33]=4[C:24]=3[CH:22]2[OH:23])[O:16][CH2:15]1)([CH3:10])([CH3:9])[CH3:8]

Participants

8

Reactant 4

HCID 8058HexaneHCID 2734941(1,1'-Binaphthalen)-2-yldi-tert-butylphosphineHCID 23665647Potassium tert-butoxideHCID 71118315HCID 71118315, compound

Product 1

HCID 86730725HCID 86730725, compoundYield 56.3%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Potassium tert-butoxide (231 mg, 2.06 mmol, 2.0 eq) is added at room temperature to a stirred solution of (3R,6S)-{[6-[3-(3-chloro-5-fluoro-6-methoxy-quinolin-4-yl)-2,3-dihydroxy-propyl]-tetrahydro-pyran-3-yl}-carbamic acid tert-butyl ester (500 mg, 1.03 mmol, 1.0 eq) in dioxane (50 mL), followed by palladium(II) acetate (93 mg, 0.41 mmol, 0.4 eq) and racemic-2-di-tert-butylphosphino-1,1′-binaphthyl (164 mg, 0.41 mmol, 0.4 eq). After 16 hours stirring at 100° C., the reaction mixture is cooled down to room temperature and filtered through decalite. The filtrate is concentrated and the crude product is purified by column chromatography (silica gel, eluent: n-hexane:ethyl acetate, 5:1, v/v) to afford (3R,6S)-[6-(9-fluoro-1-hydroxy-8-methoxy-1,2-dihydro-furo[2,3-c]quinolin-2-ylmethyl)-tetrahydro-pyran-3-yl]-carbamic acid tert-butyl ester as a yellow solid (260 mg, 56% yield).

Workup

  1. temperaturethe reaction mixture is cooled down to room temperature
  2. filtrationfiltered through decalite
  3. concentrationThe filtrate is concentrated
  4. customthe crude product is purified by column chromatography (silica gel, eluent

Sources & evidence

ORD record
ord-046d26043d024532929e0d6206320056
Source dataset
uspto-grants-2016_04
Patent number
US09321788B2

Reaction notes

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