hydroxylamine-O-sulfonic acid → HCID 178498984, compound

HRID 335515Notes

Reaction equation

HRID 335515 reaction equation
C(=O)([O-])O.[Na+].O.C(=O)([O-])O.[Na+].[NH2:12]OS(O)(=O)=O.[CH3:18][O:19][C:20]([C:22]([C:27]([O:29]C)=O)=[C:23]([S:25][CH3:26])[SH:24])=[O:21]>O>[CH3:18][O:19][C:20]([C:22]1[C:27]([OH:29])=[N:12][S:24][C:23]=1[S:25][CH3:26])=[O:21]

Participants

6

Reactant 4

HCID 76284hydroxylamine-O-sulfonic acidHCID 516892Sodium BicarbonateHCID 86585896Sodium bicarbonate waterHCID 178500975HCID 178500975, compound2×

Product 1

HCID 178498984HCID 178498984, compoundYield 73%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
25 °C

Procedure

A separate reaction vessel was charged with water (280 mL, 7 volumes) and sodium hydrogencarbonate (1.5 equiv, 38.2 g). The water/sodium hydrogencarbonate mixture was cooled to 5° C. under nitrogen atmosphere. Hydroxylamine-O-sulfonic acid (1.2 equiv, 41.1 g) was added over 5 minutes, and the mixture was stirred 15-30 minutes. The 2,2-Bis-methoxycarbonyl-1-methylsulfanyl-ethenethiol anion/acetonitrile solution from Example 1 was added over 60-70 minutes. The mixture was warmed to 25° C. over 1 hour, then held for 16 hours at 25° C. Most of the acetonitrile was removed by vacuum distillation (130 Torr, 50° C.). The residue was cooled to room temperature, acidified to pH ˜1 by addition of 37% hydrochloric acid (32 mL). The solids were granulated for 16 hours at 25° C. The slurry was filtered, and the filter cake was washed 3×100 mL with water, once with 200 mL 1:3 ethyl acetate:hexanes (v/v), and once with 100 mL 1:3 ethyl acetate:hexanes (v/v). The wet cake (50.5 g) was dried in a vacuum oven for 16 hours to give 3-Hydroxy-5-methylsulfanyl-isothiazole-4-carboxylic acid methyl ester, providing 45.4 grams (73% yield). 1H NMR: (DMSO-d6) δ 11.92 (s, 1H); 3.74 (s, 3H); 2.53 (s, 3H). MS: (API-ES pos) 206 (M+H)+, base.

Workup

  1. customA separate reaction vessel
  2. waitheld for 16 hours at 25° C
  3. customMost of the acetonitrile was removed by vacuum distillation (130 Torr, 50° C.)
  4. temperatureThe residue was cooled to room temperature
  5. additionacidified to pH ˜1 by addition of 37% hydrochloric acid (32 mL)
  6. waitThe solids were granulated for 16 hours at 25° C
  7. filtrationThe slurry was filtered
  8. washthe filter cake was washed 3×100 mL with water
  9. customThe wet cake (50.5 g) was dried in a vacuum oven for 16 hours

Sources & evidence

ORD record
ord-567b739a0ae34a3b8c702fd8b34e0946
Source dataset
uspto-grants-2014_11
Patent number
US08884025B2

Reaction notes

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