Methanesulfonyl chloride → HCID 86695405, compound

HRID 525518Notes

Reaction equation

HRID 525518 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@H:12]([CH2:13][F:14])[C@@H:11]([C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:22]=[N:23][C:24]([C:28]#[N:29])=[C:25]([F:27])[CH:26]=3)=[CH:17][CH:16]=2)[O:10][C:9]1([CH3:31])[CH3:30])=[O:7])([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+].C(N(C(C)C)CC)(C)C.[CH3:43][S:44](Cl)(=[O:46])=[O:45]>CO.Cl[Ni]Cl>[F:27][C:25]1[CH:26]=[C:21]([C:18]2[CH:17]=[CH:16][C:15]([C@H:11]3[O:10][C:9]([CH3:31])([CH3:30])[N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[C@@H:12]3[CH2:13][F:14])=[CH:20][CH:19]=2)[CH:22]=[N:23][C:24]=1[CH2:28][NH:29][S:44]([CH3:43])(=[O:46])=[O:45]

Participants

7

Reactant 4

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 4311764Sodium borohydrideHCID 86695403HCID 86695403, compound

Product 1

HCID 86695405HCID 86695405, compound

Reagents, catalysts & solvents 2

HCID 24385Nickel DichlorideCatalystHCID 887MethanolSolvent

Procedure

(4S,5R)-tert-butyl-5-(4-(6-cyano-5-fluoropyridin-3-yl)phenyl)-4-(fluoromethyl)-2,2-dimethyloxazolidine-3-carboxylate (1440 mg, 3.4 mmol) in methanol (25 mL) at 5° C. is treated with NiCl2 (80 mg, 0.34 mmol) and then sodium borohydride (380 mg, 10 mmol) is added in portions. The mixture is stirred for 1 hour at room temperature, concentrated to remove the methanol, quenched with aqueous sodium bicarbonate and extracted with ethyl acetate. The organics are dried over anhydrous sodium sulfate, filtered, and concentrated to an oil. The oil is dissolved in dichloromethane (5 mL), cooled to 5° C. and treated with diisopropylethylamine (0.88 mL, 5.0 mmol) and methanesulfonyl chloride (0.30 mL, 3.7 mmol) and stirred for 2 hours at room temperature. The mixture is concentrated and chromatographed on silica eluting with ethyl acetate in heptane to give the title compound. 1H NMR (400 MHz, CDCl3) 1.53 (s, 9H), 1.63 (s, 3H), 1.75 (s, 3H), 3.80-4.00 (m, 1H), 4.40-4.50 (m, 0.5H), 4.55-4.65 (m, 2.5H), 5.22 (d, 1H, J=7.33 Hz), 5.72 (bs, 1H), 7.60-7.70 (m, 5H), 8.63 (s, 1H). m/z (Cl) M+H 512.

Workup

  1. concentrationconcentrated
  2. customto remove the methanol
  3. customquenched with aqueous sodium bicarbonate
  4. extractionextracted with ethyl acetate
  5. dry with materialThe organics are dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to an oil
  8. dissolutionThe oil is dissolved in dichloromethane (5 mL)
  9. temperaturecooled to 5° C.
  10. stirringstirred for 2 hours at room temperature
  11. concentrationThe mixture is concentrated
  12. customchromatographed on silica eluting with ethyl acetate in heptane

Sources & evidence

ORD record
ord-95931a8adb5548249d6e13d33d54052d
Source dataset
uspto-grants-2016_05
Patent number
US09340564B2

Reaction notes

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