tert-Butyldimethylsilyl chloride → 3-{[5-(azetidin-1-ylcarbonyl)-3-chloropyridin-2-yl]oxy}-5-[((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-methylethyl)oxy]benzoic acid

HRID 1990267Notes

Reaction equation

HRID 1990267 reaction equation
[Si:1](Cl)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[N:9]1([C:13]([C:15]2[CH:16]=[C:17]([Cl:36])[C:18]([O:21][C:22]3[CH:23]=[C:24]([CH:28]=[C:29]([O:31][C@@H:32]([CH3:35])[CH2:33][OH:34])[CH:30]=3)[C:25]([OH:27])=[O:26])=[N:19][CH:20]=2)=[O:14])[CH2:12][CH2:11][CH2:10]1.N12CCCN=C1CCCCC2>C(#N)C>[N:9]1([C:13]([C:15]2[CH:16]=[C:17]([Cl:36])[C:18]([O:21][C:22]3[CH:23]=[C:24]([CH:28]=[C:29]([O:31][C@@H:32]([CH3:35])[CH2:33][O:34][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])[CH:30]=3)[C:25]([OH:27])=[O:26])=[N:19][CH:20]=2)=[O:14])[CH2:12][CH2:11][CH2:10]1

Participants

5

Reactant 3

HCID 28928tert-Butyldimethylsilyl chlorideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 591271743-{[5-(azetidin-1-ylcarbonyl)-3-chloropyridin-2-yl]oxy}-5-{[(1S)-2-hydroxy-1-methylethyl]oxy}benzoic acid

Product 1

HCID 536296873-{[5-(azetidin-1-ylcarbonyl)-3-chloropyridin-2-yl]oxy}-5-[((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-methylethyl)oxy]benzoic acidYield 60.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

tert-Butyldimethylsilyl chloride (2.78 g, 18.4 mmol) was added to a mixture of 3-{[5-(azetidin-1-ylcarbonyl)-3-chloropyridin-2-yl]oxy}-5-{[(1S)-2-hydroxy-1-methylethyl]oxy}benzoic acid (3.74 g, 9.19 mmol) and 1,8-diazabicyclo(5,4,0)undec-7-ene (2.75 mL, 7.36 mmol) in acetonitrile (40 mL) and stirred at RT for 24 hours. The solvent was removed in vacuo and water (80 mL) added to the resultant oil. The mixture was adjusted to pH 10 with 1M sodium bicarbonate solution and washed with ether to remove any impurities. The aqueous layer was adjusted to pH 3 with 1M citric acid and extracted into ethyl acetate (2×100 mL). The combined organics were washed with brine (50 mL), dried (MgSO4), filtered and reduced in vacuo to give the desired compound as a white foam (2.9 g).

Workup

  1. customThe solvent was removed in vacuo and water (80 mL)
  2. additionadded to the resultant oil
  3. washwashed with ether
  4. customto remove any impurities
  5. extractionextracted into ethyl acetate (2×100 mL)
  6. washThe combined organics were washed with brine (50 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered

Sources & evidence

ORD record
ord-3e56299181f546f796eead76729945f0
Source dataset
uspto-grants-2010_01
Patent number
US07642259B2

Reaction notes

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