Water → HCID 86746738, compound

HRID 1938187Notes

Reaction equation

HRID 1938187 reaction equation
[CH3:1][C:2]1([CH3:28])[CH:6]2[CH2:7][CH2:8][C@@:3]1([CH2:10][S:11]([N:14]1[CH2:19][CH2:18][C:17]3([C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[CH:21]=[CH:20]3)[CH2:16][CH2:15]1)(=[O:13])=[O:12])[C:4](=O)[CH2:5]2.Cl.[NH2:30][OH:31].O>N1C=CC=CC=1>[CH3:1][C:2]1([CH3:28])[CH:6]2[CH2:7][CH2:8][C@@:3]1([CH2:10][S:11]([N:14]1[CH2:19][CH2:18][C:17]3([C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[CH:21]=[CH:20]3)[CH2:16][CH2:15]1)(=[O:13])=[O:12])[C:4](=[N:30][OH:31])[CH2:5]2

Participants

5

Reactant 3

HCID 962WaterHCID 443297Hydroxyamine hydrochloride3×HCID 44351086HCID 44351086, compound

Product 1

HCID 86746738HCID 86746738, compoundYield 90.1%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

(1S)-1'-(((7,7-dimethyl-2-oxobicyclo(2.2.1) hept-1-yl)methyl)sulfonyl)spiro(1H-indene-1,4'-piperidine) (30 g, 0.075 mole) in pyridine (500 mL) was heated in an oil bath to 70° C. (internal). Hydroxylamine hydrochloride (30 g) was added in three portions over ca. 20 minutes. After 2 hours, an additional 10 g of hydroxylamine hydrochloride was added (over 10 minutes). At 30, 40, and 50 minutes additional elapsed time, further 3 g lots of hydroxylamine hydrochloride were added. After another 30 minutes, the mixture was poured into water (2 L) and extracted 3 times with ethyl acetate (300 mL portions). The organic layers were combined, washed with 1N HCl (600 mL total), dried over sodium sulfate, filtered, and evaporated to dryness in vacuo. EtOH (abs; ca. 250 mL) was added to the resulting thick syrup and the solution allowed to stand at ambient temperature overnight. The mixture was filtered and the filtrate boiled down to ca. 80 mL. After standing, the mixture was again filtered and boiled down to ca. 20 mL. After a third filtration, the filtered solids were combined to give (1S)-1'-(((7,7-dimethyl-2-oximinobicyclo(2.2.1)hept-1-yl)-methyl) sulfonyl)spiro(1H-indene-1,4'-piperidine) (28 g).

Workup

  1. customAt 30, 40, and 50 minutes
  2. additionwere added
  3. waitAfter another 30 minutes
  4. extractionextracted 3 times with ethyl acetate (300 mL portions)
  5. washwashed with 1N HCl (600 mL total)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated to dryness in vacuo
  9. additionEtOH (abs; ca. 250 mL) was added to the resulting thick syrup
  10. waitto stand at ambient temperature overnight
  11. filtrationThe mixture was filtered
  12. filtrationthe mixture was again filtered
  13. filtrationAfter a third filtration

Sources & evidence

ORD record
ord-29afa264b2814f8e92154d4bc1ee944a
Source dataset
uspto-grants-1997_12
Patent number
US05693643

Reaction notes

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