HCID 87481358, compound → tert-Butylammonium (S)-(-)-2-{[2-(4-hydroxyphenyl)ethyl]thio}-3-[4-(2-{4-[(methylsulfonyl)oxy]phenoxy}ethyl)phenyl]propanoate

HRID 1716184Notes

Reaction equation

HRID 1716184 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][S:10][CH:11]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([CH2:22][CH2:23][O:24][C:25]3[CH:30]=[CH:29][C:28]([O:31][S:32]([CH3:35])(=[O:34])=[O:33])=[CH:27][CH:26]=3)=[CH:18][CH:17]=2)[C:12]([O-:14])=[O:13])=[CH:4][CH:3]=1.[C:36]([NH3+:40])([CH3:39])([CH3:38])[CH3:37]>C(O)C>[OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][S:10][C@@H:11]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([CH2:22][CH2:23][O:24][C:25]3[CH:26]=[CH:27][C:28]([O:31][S:32]([CH3:35])(=[O:34])=[O:33])=[CH:29][CH:30]=3)=[CH:18][CH:17]=2)[C:12]([O-:14])=[O:13])=[CH:4][CH:3]=1.[C:36]([NH3+:40])([CH3:39])([CH3:38])[CH3:37]

Participants

3

Reactant 1

HCID 87481358HCID 87481358, compound

Product 1

HCID 86620207tert-Butylammonium (S)-(-)-2-{[2-(4-hydroxyphenyl)ethyl]thio}-3-[4-(2-{4-[(methylsulfonyl)oxy]phenoxy}ethyl)phenyl]propanoateYield 87.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

Crude tert-Butylammonium 2-{[2-(4-hydroxyphenyl)ethyl]thio}-3-[4-(2-{4-[(methylsulfonyl)oxy]phenoxy}ethyl)phenyl]propanoate (11.7 g, 19.8 mmol) was stirred in warm absolute ethanol (53.8 mL) at 71° C. to achieve complete dissolution. The resulting solution was screened into a second vessel through a 1 μm filter, followed by a line wash of warm ethanol (4.7 mL), and the solution allowed to cool to 60° C. Seed crystals (60 mg, 0.5% w/w) were added as a slurry in ethanol (0.5 mL) and the solution held at 60° C. for 30 minutes before cooling to 51° C. at 0.1° C./minute. The solution was held at 51° C. for 3 hours, during which period further seed crystals formed. The slurry was cooled to 46° C. at 0.1° C./minute, and held for 3 hours; then to 41° C. at 0.1° C./minute, and held for 3 hours; then to 31° C. at 0.1° C./minute, and held for 2 hours; then to 17° C. at 0.17° C./minute, and held for at least 5-6 hours. The solid was isolated by filtration, washed by displacement with absolute ethanol (11.7 mL) and dried in a vacuum oven at 50° C. to yield the title compound as a white solid (10.2 g, 87%). HPLC (Rt 9.8 min); chiral HPLC (typically 98% e.e.); mp 137-139° C.; MS (ES+) 534 (M+NH4+, 20%), 517 (M+H+, 30%), 471 (M-CO2H+, 100%). Other data as noted for the Crude stage above.

Workup

  1. dissolutiondissolution
  2. customThe resulting solution was screened into a second vessel through a 1 μm
  3. filtrationfilter
  4. washwash of warm ethanol (4.7 mL)
  5. additionSeed crystals (60 mg, 0.5% w/w) were added as a slurry in ethanol (0.5 mL)
  6. temperaturebefore cooling to 51° C. at 0.1° C./minute
  7. waitThe solution was held at 51° C. for 3 hours, during which period further seed crystals
  8. customformed
  9. temperatureThe slurry was cooled to 46° C. at 0.1° C./minute
  10. waitheld for 3 hours
  11. waitthen to 41° C. at 0.1° C./minute, and held for 3 hours
  12. waitthen to 31° C. at 0.1° C./minute, and held for 2 hours
  13. waitthen to 17° C. at 0.17° C./minute, and held for at least 5-6 hours
  14. customThe solid was isolated by filtration
  15. washwashed by displacement with absolute ethanol (11.7 mL)
  16. customdried in a vacuum oven at 50° C.

Sources & evidence

ORD record
ord-bfbab793f3664283ae9f7d71a03075f0
Source dataset
uspto-grants-2010_09
Patent number
US07803586B2

Reaction notes

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