1,2-Dichlorobenzene → HCID 117986066, compound

HRID 1055592Notes

Reaction equation

HRID 1055592 reaction equation
C([O:8][C@H:9]1[C@H:15]([O:16]CC2C=CC=CC=2)[C@@H:14]([O:24]CC2C=CC=CC=2)[C@:13]2([C:33]3[CH:38]=[CH:37][C:36]([Cl:39])=[C:35]([CH2:40][C:41]4[CH:46]=[CH:45][C:44]([O:47][CH2:48][CH3:49])=[C:43]([F:50])[C:42]=4[F:51])[CH:34]=3)[O:32][C@@:10]1([CH:52]([OH:54])[CH3:53])[CH2:11][O:12]2)C1C=CC=CC=1.ClC1C=CC=CC=1Cl>[Pd].CO.O1CCCC1>[Cl:39][C:36]1[CH:37]=[CH:38][C:33]([C@@:13]23[O:32][C@@:10]([CH:52]([OH:54])[CH3:53])([CH2:11][O:12]2)[C@@H:9]([OH:8])[C@H:15]([OH:16])[C@H:14]3[OH:24])=[CH:34][C:35]=1[CH2:40][C:41]1[CH:46]=[CH:45][C:44]([O:47][CH2:48][CH3:49])=[C:43]([F:50])[C:42]=1[F:51]

Participants

5

Reactant 2

HCID 72391,2-DichlorobenzeneHCID 131736391HCID 131736391, compound

Product 1

HCID 117986066HCID 117986066, compoundYield 43.5%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 21899815MeOH tetrahydrofuranSolvent

Procedure

To a solution of 1-[(1R,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[4-chloro-3-[(4-ethoxy-2,3-difluoro-phenyl)methyl]phenyl]-6,8-dioxabicyclo[3.2.1]octan-1-yl]ethanol 23p (530 mg, 0.67 mmol) in a methanol/tetrahydrofuran mixture (v/v=4/1, 10 mL) were added o-dichlorobenzene (0.4 mL, 3.5 mmol) and 10% Pd/C (212 mg, 0.2 mmol) at room temperature. The mixture was stirred at room temperature for 4 hours under H2 and filtered. The filtrate was concentrated in vacuo and the residue was purified by silica gel chromatography eluted with PE/EtOAc(v/v)=3/1 to give a few white solid. Then the solid was further purified by prep-HPLC to give the title compound 23 as a white solid (142 mg, 43%, HPLC: 97.3%). The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 487.1 [M+H]+; and 1H NMR (600 MHz, CDCl3) δ(ppm): 7.43-7.36 (m, 1H), 7.33 (m, 2H), 6.72 (m, 1H), 6.60 (m, 1H), 4.25-4.17 (m, 1H), 4.03 (m, 4H), 3.95 (m, 1H), 3.87 (m, 1H), 3.75 (m, 3H), 1.42 (t, 3H), 1.27 (d, 3H).

Workup

  1. filtrationfiltered
  2. concentrationThe filtrate was concentrated in vacuo
  3. customthe residue was purified by silica gel chromatography
  4. washeluted with PE/EtOAc(v/v)=3/1
  5. customto give a few white solid
  6. customThen the solid was further purified by prep-HPLC

Sources & evidence

ORD record
ord-ff400273b4ec4b4ab8d70d0ab86f42ae
Source dataset
uspto-grants-2016_07
Patent number
US09394329B2

Reaction notes

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