Sulfuric Acid → (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[1,2,3]triazol-1-yl]-phenyl}-propionic acid tert-butyl ester

HRID 1265588Notes

Reaction equation

HRID 1265588 reaction equation
CO[C:3](=[O:23])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([N:10]2[C:14]([CH2:15][O:16][CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][O:18]3)=[CH:13][N:12]=[N:11]2)[CH:5]=1.N(C1C=C(C=CC=1)C(OC)=O)=[N+]=[N-].C([Si](C)(C)C#CCOC1CCCCO1)(C)(C)C.OS(O)(=O)=O.O1C=CCCC1.CC1C=CC(S(O)(=O)=O)=CC=1.O.[C:77]([O:80][C:81]([CH3:84])([CH3:83])[CH3:82])(=[O:79])[CH3:78].[Li]>CCCC[N+](CCCC)(CCCC)CCCC.[F-].Cl.CO.C(Cl)Cl>[C:81]([O:80][C:77](=[O:79])[CH2:78][C:3](=[O:23])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([N:10]2[C:14]([CH2:15][O:16][CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][O:18]3)=[CH:13][N:12]=[N:11]2)[CH:5]=1)([CH3:84])([CH3:83])[CH3:82]

Participants

12

Reactant 7

HCID 1118Sulfuric AcidHCID 80803,4-dihydro-2H-pyranHCID 521998p-Toluenesulfonic acid monohydrateHCID 11240787Methyl 3-azidobenzoateHCID 12048027(RS)-3-[5-(tetrahydro-pyran-2-yloxymethyl)-[1,2,3]triazol-1-yl]-benzoic acid methyl esterHCID 15696080(RS)-tert.-butyl-dimethyl-[3-(tetrahydro-pyran-2-yloxy)-prop-1-ynyl]-silaneHCID 86586795Lithium Tert-butyl Acetate

Product 1

HCID 12048028(RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[1,2,3]triazol-1-yl]-phenyl}-propionic acid tert-butyl ester

Reagents, catalysts & solvents 4

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 2724141Tetrabutylammonium FluorideSolvent

Procedure

The title compound was prepared from (RS)-3-[5-(tetrahydro-pyran-2-yloxymethyl)-[1,2,3]triazol-1-yl]-benzoic acid methyl ester [prepared by the following sequence: i.) methyl 3-azidobenzoate [CAS-No. 93066-93-4] (15.55 g, 88 mmol) and (RS)-tert.-butyl-dimethyl-[3-(tetrahydro-pyran-2-yloxy)-prop-1-ynyl]-silane [CAS-No. 135294-85-8] (33.50 g, 132 mmol) were heated to 60° C. for 10 days; ii.) The obtained material (48.2 g, ca. 88 mmol) was stirred in TBAF (300 mL, 1M in THF) at 70° C. for 6 days and subsequently refluxed in 1N HCl (400 mL) for 2 h; iii.) The obtained material (16.15 g, 74 mmol) was stirred in MeOH (400 mL) and conc. H2SO4 (30 mL) at 23° C. for 11 days. iv.) Part of the obtained material (4.60 g, 19.7 mmol) was reacted with 3,4-dihydro-2H-pyran (2.67 mL, 29.5 mmol) and cat. amount p-TsOH.H2O in DCM (38 mL) at 23° C. for 20 h.] (6.20 g, 19.5 mmol) by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (8.47 g).

Workup

  1. customprepared by the following sequence
  2. customat 23° C.
  3. customfor 20 h.

Sources & evidence

ORD record
ord-8cf91fad45ba45d4aa9b97a8fa280882
Source dataset
uspto-grants-2003_04
Patent number
US06544985B2

Reaction notes

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