Hydrochloric Acid → (2S,3R,6S)-4-[4-(4-Hydroxy-4-methyl-pent-2-ynyloxy)-benzenesulfonyl]-2,6-dimethyl-morpholine-3-carboxylic acid hydroxyamide

HRID 1935341Notes

Reaction equation

HRID 1935341 reaction equation
Cl.[NH2:2][OH:3].[OH-].[K+].C[O:7][C:8]([C@H:10]1[C@H:15]([CH3:16])[O:14][C@@H:13]([CH3:17])[CH2:12][N:11]1[S:18]([C:21]1[CH:26]=[CH:25][C:24]([O:27][CH2:28][C:29]#[C:30][C:31]([OH:34])([CH3:33])[CH3:32])=[CH:23][CH:22]=1)(=[O:20])=[O:19])=O.Cl>CO>[OH:3][NH:2][C:8]([C@H:10]1[C@H:15]([CH3:16])[O:14][C@@H:13]([CH3:17])[CH2:12][N:11]1[S:18]([C:21]1[CH:26]=[CH:25][C:24]([O:27][CH2:28][C:29]#[C:30][C:31]([OH:34])([CH3:33])[CH3:32])=[CH:23][CH:22]=1)(=[O:20])=[O:19])=[O:7]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 443297Hydroxyamine hydrochlorideHCID 12016682(2S,3R,6S)-4-[4-(4-hydroxy-4-methyl-pent-2-ynyloxy)-benzenesulfonyl]-2,6-dimethyl-morpholine-3-carboxylic acid methyl ester

Product 1

HCID 12016681(2S,3R,6S)-4-[4-(4-Hydroxy-4-methyl-pent-2-ynyloxy)-benzenesulfonyl]-2,6-dimethyl-morpholine-3-carboxylic acid hydroxyamideYield 21.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
85 °C

Procedure

Hydroxylamine hydrochloride (2.76 g, 39.7 mmol) was dissolved in methanol (14 mL) by heating to 85° C. This solution was added to a solution of potassium hydroxide (3.31 g, 59.0 mmol) in methanol (8.3 mL) and the resulting white slurry stirred for 15 minutes. The white precipitate was removed by filtration and the filtrate was added to a flask containing (2S,3R,6S)-4-[4-(4-hydroxy-4-methyl-pent-2-ynyloxy)-benzenesulfonyl]-2,6-dimethyl-morpholine-3-carboxylic acid methyl ester (258 mg, 0.607 mmol) and the reaction was stirred at room temperature for 1.5 hours. 1 N hydrochloric acid (20 mL) was then added drop wise and the methanol was removed in vacuo. The aqueous residue was extracted with ethyl acetate (3×50 mL) and the combined organic fractions were washed with brine ( 30 mL), dried over anhydrous magnesium sulfate and concentrated in vacuo. The resulting white solid was chromatographed on a Biotage column® (40s) eluting with ethyl acetate and hexanes (7:1, the column was pretreated with 0.5% triethyl amine in above solvent system) to yield the title compound (54.8 mg, 21%, 2 steps). MS: Calculated for C19H26N2O7S (M+H): 427.16 and (M−H): 425.14. Found: 427.0 and 425.2.

Workup

  1. customThe white precipitate was removed by filtration
  2. additionthe filtrate was added to a flask
  3. stirringthe reaction was stirred at room temperature for 1.5 hours
  4. customthe methanol was removed in vacuo
  5. extractionThe aqueous residue was extracted with ethyl acetate (3×50 mL)
  6. washthe combined organic fractions were washed with brine ( 30 mL)
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated in vacuo
  9. customThe resulting white solid was chromatographed on a Biotage column® (40s)
  10. washeluting with ethyl acetate and hexanes (7:1

Sources & evidence

ORD record
ord-9d620fd581da4d4f932eb47fa1d4239b
Source dataset
uspto-grants-2002_05
Patent number
US06387901B1

Reaction notes

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