Sodium borohydride → HCID 46202633, compound

HRID 1644751Notes

Reaction equation

HRID 1644751 reaction equation
[Cl:1][C:2]1[CH:24]=[C:23]([S:25]([CH3:28])(=[O:27])=[O:26])[CH:22]=[CH:21][C:3]=1[C:4]([C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([F:16])[CH:14]=2)[CH:9]=[C:8]([CH2:17][C:18]([OH:20])=[O:19])[CH:7]=1)=[O:5].[BH4-].[Na+]>CO>[Cl:1][C:2]1[CH:24]=[C:23]([S:25]([CH3:28])(=[O:26])=[O:27])[CH:22]=[CH:21][C:3]=1[CH:4]([OH:5])[C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([F:16])[CH:14]=2)[CH:9]=[C:8]([CH2:17][C:18]([OH:20])=[O:19])[CH:7]=1

Participants

4

Reactant 2

HCID 4311764Sodium borohydride2×HCID 46204573HCID 46204573, compound

Product 1

HCID 46202633HCID 46202633, compoundYield 54%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of [4-(2-chloro-4-methanesulfonyl-benzoyl)-6-fluoro-naphthalen-2-yl]-acetic acid (example 2-8) (920 mg, 2.19 mmol) in methanol (20 mL) was added sodium borohydride (248 mg, 6.56 mmol) at 0° C. The mixture was stirred at 0° C. for 30 minutes before warming to room temperature. After 4 hours, the reaction was once again cooled to 0° C., and additional sodium borohydride (163 mg, 4.31 mmol) was added. The reaction mixture was then warmed to room temperature, and stirred at room temperature overnight. The solvent was removed under reduced pressure. The residue was dissolved in ethyl acetate and washed once with a 0.5 N hydrochloric acid solution. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. Reverse phase preparative HPLC (using a Waters® Delta-Prep™ 3000 with a Varian Pursuit® C-18 column [10 μm, 20×150 mm]) gave {4-[(2-chloro-4-methanesulfonyl-phenyl)-hydroxy-methyl]-6-fluoro-naphthalen-2-yl}-acetic acid (500 mg, 54%) as an off-white powder. 1H NMR (300 MHz, 1.8:1 mixture of CD3OD and CDCl3) δ ppm 7.92 (s, 1 H), 7.75-7.85 (m, 3 H), 7.62-7.71 (m, 2 H), 7.16-7.29 (m, 2 H), 6.70 (s, 1 H), 3.64 (s, 2 H), 3.09 (s, 3 H); HRMS (ESI+) cald. for C20H16ClFO5S [(M+Na)+] 445.0283, obsd. 445.0281.

Workup

  1. temperaturebefore warming to room temperature
  2. waitAfter 4 hours
  3. temperaturethe reaction was once again cooled to 0° C.
  4. temperatureThe reaction mixture was then warmed to room temperature
  5. stirringstirred at room temperature overnight
  6. customThe solvent was removed under reduced pressure
  7. dissolutionThe residue was dissolved in ethyl acetate
  8. washwashed once with a 0.5 N hydrochloric acid solution
  9. dry with materialThe organic layer was dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f893b7acd2874a68864a061fa65d0374
Source dataset
uspto-grants-2012_02
Patent number
US08124629B2

Reaction notes

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