1,2-Dichlorobenzene → HCID 117986064, compound

HRID 1055562Notes

Reaction equation

HRID 1055562 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])[CH:42]=4)[CH:34]=3)[O:32][C@@:10]1([CH:51]([OH:53])[CH3:52])[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:51]([OH:53])[CH3:52])([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])[CH:42]=1

Participants

5

Reactant 2

HCID 72391,2-DichlorobenzeneHCID 118377853HCID 118377853, compound

Product 1

HCID 117986064HCID 117986064, compoundYield 36.5%

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-3-fluoro-phenyl) methyl]phenyl]-6,8-dioxabicyclo[3.2.1]octane-1-yl]ethanol 19c (2.16 g, 2.92 mmol) in a methanol/tetrahydrofuran mixture (v/v=4/1, 20 mL) were added o-dichlorobenzene (1.64 mL, 14.6 mmol) and 10% Pd/C (0.5 g, 0.42 mmol) in turn at room temperature. The mixture was stirred at room temperature for 3 hours under H2 and filtered. The filter cake was washed with a tetrahydrofuran/methanol mixture (v/v=1/4, 10 mL×2). The filtrate was concentrated in vacuo. The residue was purified by prep-HPLC to give the title compound 19 as a white solid (0.5 g, 36.5%, HPLC: 96.7%). The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: MS (ESI, pos. ion) m/z: 469.2[M+H]+; and 1H NMR (400 MHz, DMSO-d6) δ(ppm): 7.42 (m, 1H), 7.39 (s, 1H), 7.31 (dd, 1H), 7.05 (d, 1H), 7.02 (m, 1H), 6.92 (d, 1H), 5.27 (d, 1H), 4.98 (d, 1H), 4.89 (d, 1H), 4.60 (d, 1H), 4.02 (m, 2H), 3.99 (m, 3H), 3.84 (m, 1H), 3.76 (d, 1H), 3.53 (m, 1H), 3.43 (m, 1H), 3.38 (m, 1H), 1.31 (t, 3H), 1.16 (d, 3H).

Workup

  1. filtrationfiltered
  2. washThe filter cake was washed with a tetrahydrofuran/methanol mixture (v/v=1/4, 10 mL×2)
  3. concentrationThe filtrate was concentrated in vacuo
  4. customThe residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-62cbed56c7f9432f809476ba2806089b
Source dataset
uspto-grants-2016_07
Patent number
US09394329B2

Reaction notes

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