2-Methylbenzenesulfonic acid → (1S,2S,3S,4R,5S)-5-[4-chloro-3-(4-hydroxy-benzyl)-phenyl]-1-hydroxymethyl-6,8-dioxa-bicyclo[3.2.1]octane-2,3,4-triol

HRID 59211

Reaction equation

HRID 59211 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@:8]2(OC)[C@H:13]([OH:14])[C@@H:12]([OH:15])[C@H:11]([OH:16])[C:10]([CH2:19][OH:20])([CH2:17][OH:18])[O:9]2)=[CH:4][C:3]=1[CH2:23][C:24]1[CH:29]=[CH:28][C:27]([OH:30])=[CH:26][CH:25]=1.CC1CCCO1.C1(C)C(S(O)(=O)=O)=CC=CC=1>ClCCl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@:8]23[O:9][C@@:10]([CH2:19][OH:20])([CH2:17][O:18]2)[C@@H:11]([OH:16])[C@H:12]([OH:15])[C@H:13]3[OH:14])=[CH:4][C:3]=1[CH2:23][C:24]1[CH:25]=[CH:26][C:27]([OH:30])=[CH:28][CH:29]=1

Participants

5

Reactant 3

HCID 69252-Methylbenzenesulfonic acidHCID 73012-MethyltetrahydrofuranHCID 67154050(2S,3R,4S,5S)-2-[4-Chloro-3-(4-hydroxy-benzyl)-phenyl]-6,6-bis-hydroxymethyl-2-methoxy-tetrahydro-pyran-3,4,5-triol

Product 1

HCID 67153906(1S,2S,3S,4R,5S)-5-[4-chloro-3-(4-hydroxy-benzyl)-phenyl]-1-hydroxymethyl-6,8-dioxa-bicyclo[3.2.1]octane-2,3,4-triolYield 69.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (2S,3R,4S,5S)-2-[4-Chloro-3-(4-hydroxy-benzyl)-phenyl]-6,6-bis-hydroxymethyl-2-methoxy-tetrahydro-pyran-3,4,5-triol (580 mg, 1.32 mmol) in a mixture of dichloromethane (5 mL) of and 2-methyl-tetrahydrofuran (5 mL) was added Silicycle® Si-Tosic acid derivatized silica gel (40-63 micrometer, 0.68 mmol/g) Silicagel bound toluenesulfonic acid (1 g) and the reaction mixture was allowed to stir at room temperature overnight (˜16 hours). The mixture was filtered through a plug of Celite® and the plug rinsed with dichloromethane:2-methyl-tetrahydrofuran (40 mL; 1:1 volume). The crude material was purified by preparative HPLC on a Phenomenex Gemini NX 150×21.2 5 mm column eluting with a flow rate of 28 mL/minute; mobile phases A: water with 1% ammonium hydroxide modifier and B: methanol with 1% ammonium hydroxide modifier. The product was eluted using a gradient of 5% methanol with 1% ammonium hydroxide modifier for 1.5 minutes and increased in a linear gradient to 100% methanol with 1% ammonium hydroxide modifier over 8.5 minutes to give the product (375 mg; 69.7% yield, retention time=9.8 minute). LCMS 407 (M−H+, negative mode). 1H NMR (500 MHz, METHANOL-d4) delta ppm 3.56 (d, J=7.8 Hz, 1 H), 3.61 (d, J=7.3 Hz, 1 H), 3.66 (t, J=8.2 Hz, 1 H), 3.69 (d, J=12.4 Hz, 1H), 3.79 (d, J=8.3 Hz, 1 H), 3.85 (d, J=12.4 Hz, 1 H), 4.01 (s, 2 H), 4.16 (d, J=7.3 Hz, 1 H), 6.69 (d, J=8.3 Hz, 2 H), 7.02 (d, J=8.3 Hz, 2 H), 7.34-7.37 (m, 1 H), 7.37-7.41 (m, 1 H), 7.45 (d, J=1.5 Hz, 1 H).

Workup

  1. filtrationThe mixture was filtered through a plug of Celite®
  2. washthe plug rinsed with dichloromethane
  3. customThe crude material was purified by preparative HPLC on a Phenomenex Gemini NX 150×21.2 5 mm column
  4. washeluting with a flow rate of 28 mL/minute
  5. washThe product was eluted
  6. customfor 1.5 minutes
  7. temperatureincreased in a linear gradient to 100% methanol with 1% ammonium hydroxide modifier over 8.5 minutes
  8. customto give the product (375 mg; 69.7% yield, retention time=9.8 minute)

Sources & evidence

ORD record
ord-cdcecc1e293b4943b32d8d34ac5c327f
Source dataset
uspto-grants-2016_09
Patent number
US09439902B2

Linked notes

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