Phosphorus oxychloride → HCID 86727175, compound

HRID 579353Notes

Reaction equation

HRID 579353 reaction equation
[CH3:1][C:2]1([CH3:14])[CH2:7][CH:6]([CH2:8][C:9](O)=O)[CH2:5][C:4]([CH3:13])([CH3:12])[NH:3]1.[NH:15]([C:17](=[S:19])[NH2:18])[NH2:16].O=P(Cl)(Cl)Cl>>[CH3:1][C:2]1([CH3:14])[CH2:7][CH:6]([CH2:8][C:9]2[S:19][C:17]([NH2:18])=[N:15][N:16]=2)[CH2:5][C:4]([CH3:13])([CH3:12])[NH:3]1

Participants

4

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 2723789ThiosemicarbazideHCID 3877384(2,2,6,6-Tetramethylpiperidin-4-yl)acetic acid

Product 1

HCID 86727175HCID 86727175, compoundYield 22.5%

Conditions

Temperature
78 °C

Procedure

A stirred mixture of 2-(2,2,6,6-tetramethylpiperidin-4-yl)acetic acid (410 mg, 2.057 mmol) and hydrazinecarbothioamide (281 mg, 3.09 mmol) was cooled under nitrogen in an ice bath. POCl3 (0.575 mL, 6.17 mmol) was added drop-wise and the mixture was heated at 78° C. for 3 hours. The reaction mixture was cooled in an ice bath and quenched by addition of ice water (20 mL). The resulting mixture was sonicated for 20 minutes and the resulting suspension was stirred at room temperature for 72 hours. The resulting solution was basified by addition of NaOH (pellets added portion-wise over ˜15 minutes). The resulting suspension was stirred at room temperature for 1 hour before filtering under vacuum and rinsing with water to afford the title compound as a pale brown solid (118 mg, 22% yield). LC-MS: Rt 0.44 min; MS m/z 255.3 [M+H]+ [Method A]. 1H NMR (400 MHz, DMSO-d6) δ ppm 6.98 (s, 2H), 2.66 (d, J=7.07 Hz, 2H), 2.03 (br. s., 1H), 1.49 (d, J=10.61 Hz, 2H), 1.08 (s, 6H), 0.99 (br. s., 6H), 0.78 (t, J=12.13 Hz, 2H).

Workup

  1. temperaturewas cooled under nitrogen in an ice bath
  2. temperatureThe reaction mixture was cooled in an ice bath
  3. customquenched by addition of ice water (20 mL)
  4. customThe resulting mixture was sonicated for 20 minutes
  5. additionThe resulting solution was basified by addition of NaOH (pellets added portion-wise over ˜15 minutes)
  6. stirringThe resulting suspension was stirred at room temperature for 1 hour
  7. filtrationbefore filtering under vacuum
  8. washrinsing with water

Sources & evidence

ORD record
ord-b4861f4b44874cbb8c6f0d41823b3e68
Source dataset
uspto-grants-2015_05
Patent number
US09040712B2

Reaction notes

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