Water → (3-{[[4-(2-Hydroxy-1,1-dimethyl-ethyl)-benzyl]-(pyridine-3-sulfonyl)-amino]-methyl}-phenoxy)-acetic acid tert-butyl ester

HRID 23797

Reaction equation

HRID 23797 reaction equation
[C:1]([O:5][C:6](=[O:45])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][N:16]([CH2:26][C:27]2[CH:32]=[CH:31][C:30]([C:33]([CH3:44])([CH3:43])[CH2:34][O:35][Si](C(C)(C)C)(C)C)=[CH:29][CH:28]=2)[S:17]([C:20]2[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=2)(=[O:19])=[O:18])[CH:10]=1)([CH3:4])([CH3:3])[CH3:2].[F-].C([N+](CCCC)(CCCC)CCCC)CCC.O.C(Cl)Cl>C1COCC1>[C:1]([O:5][C:6](=[O:45])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][N:16]([CH2:26][C:27]2[CH:28]=[CH:29][C:30]([C:33]([CH3:44])([CH3:43])[CH2:34][OH:35])=[CH:31][CH:32]=2)[S:17]([C:20]2[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=2)(=[O:19])=[O:18])[CH:10]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 962WaterHCID 6344DichloromethaneHCID 2724141Tetrabutylammonium Fluoride3×HCID 69729909(3-{[{4-[2-(tert-Butyl-dimethyl-silanyloxy)-1,1-dimethyl-ethyl]-benzyl}-(pyridine-3-sulfonyl)-amino]-methyl}-phenoxy)-acetic acid tert-butyl ester

Product 1

HCID 69731661(3-{[[4-(2-Hydroxy-1,1-dimethyl-ethyl)-benzyl]-(pyridine-3-sulfonyl)-amino]-methyl}-phenoxy)-acetic acid tert-butyl esterYield 62.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (3-{[{4-[2-(tert-butyl-dimethyl-silanyloxy)-1,1-dimethyl-ethyl]-benzyl}-(pyridine-3-sulfonyl)-amino]-methyl}-phenoxy)-acetic acid tert-butyl ester (210 mg, 0.321 mmol) in THF (2 mL) was added tetrabutylammonium fluoride (1M in THF, 0.34 mL, 0.34 mmol). The reaction was heated at reflux for 1 h and additional tetrabutylammonium fluoride (1M in THF, 0.34 mL, 0.34 mmol) was added. The reaction was heated at reflux for 24 h and additional tetrabutylammonium fluoride (1M in THF, 0.34 mL, 0.34 mmol) was added. The reaction was heated for 45 minutes and was cooled to room temperature. Water and CH2Cl2 were added and the layers were separated. The aqueous solution was washed with CH2Cl2 (3×). The combined organic layers were dried (MgSO4), filtered and concentrated. Medium pressure chromatography (1:1 hexanes:EtOAc to 3:2 EtOAc: hexanes) provided (3-{[[4-(2-hydroxy-1,1-dimethyl-ethyl)-benzyl]-(pyridine-3-sulfonyl)-amino]-methyl}-phenoxy)-acetic acid tert-butyl ester (108 mg). MS 541 (M+1).

Workup

  1. temperatureThe reaction was heated
  2. temperatureat reflux for 1 h
  3. temperatureThe reaction was heated
  4. temperatureat reflux for 24 h
  5. temperatureThe reaction was heated for 45 minutes
  6. customthe layers were separated
  7. washThe aqueous solution was washed with CH2Cl2 (3×)
  8. dry with materialThe combined organic layers were dried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-75b82d6a57864c85a68908fbf20a139d
Source dataset
uspto-grants-2005_02
Patent number
US06852863B2

Linked notes

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