2-[2-(tert-Butyldimethylsilanyloxy)ethoxymethyl]thiazole → 7-{2-[2-(tert-Butyldimethylsilanyloxy)ethoxymethyl]thiazol-5-yl}-3,9-diazabicyclo[3.3.1]non-6-ene-3,6,9-tricarboxylic acid 3,9-di-tert-butyl ester 6-methyl ester

HRID 1096875Notes

Reaction equation

HRID 1096875 reaction equation
[Li]CCCC.[Si:6]([O:13][CH2:14][CH2:15][O:16][CH2:17][C:18]1[S:19][CH:20]=[CH:21][N:22]=1)([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7].[CH3:23][O:24][C:25]([C:27]1[CH:28]2[N:43]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH:32]([CH2:33][C:34]=1OS(C(F)(F)F)(=O)=O)[CH2:31][N:30]([C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[CH2:29]2)=[O:26]>C1COCC1.[Cl-].[Cl-].[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:23][O:24][C:25]([C:27]1[CH:28]2[N:43]([C:44]([O:46][C:47]([CH3:50])([CH3:48])[CH3:49])=[O:45])[CH:32]([CH2:33][C:34]=1[C:20]1[S:19][C:18]([CH2:17][O:16][CH2:15][CH2:14][O:13][Si:6]([C:9]([CH3:12])([CH3:10])[CH3:11])([CH3:7])[CH3:8])=[N:22][CH:21]=1)[CH2:31][N:30]([C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[CH2:29]2)=[O:26]

Participants

7

Reactant 3

HCID 667839212-[2-(tert-Butyldimethylsilanyloxy)ethoxymethyl]thiazoleHCID 866370767-Trifluoromethanesulfonyloxy-3,9-diazabicyclo[3.3.1]non-6-ene-3,6,9-tricarboxylic acid 3,9-di-tert-butyl ester 6-methyl esterHCID 178418339Butyllithium

Product 1

HCID 866370787-{2-[2-(tert-Butyldimethylsilanyloxy)ethoxymethyl]thiazol-5-yl}-3,9-diazabicyclo[3.3.1]non-6-ene-3,6,9-tricarboxylic acid 3,9-di-tert-butyl ester 6-methyl esterYield 65%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

BuLi (1.6 M in hexane, 5.70 mL, 9.05 mmol) was added dropwise to a cooled (−78° C.) solution of 2-[2-(tert-butyldimethylsilanyloxy)ethoxymethyl]thiazole (1.900 g, 6.786 mmol) in THF (15 mL). The reaction mixture was stirred at −78° C. for 1 h, and ZnCl2 (1M in THF, 11.3 mL, 11.3 mmol) was added dropwise at −78° C. The cooling bath was removed, and the reaction mixture was stirred for 1 h at rt. A sol. of compound Y (2.00 g, 3.77 mmol) in THF (5 mL) was added dropwise, followed by Pd(PPh3)4 (136 mg, 0.109 mmol). The reaction mixture was stirred at rt for 2 h, partitioned between EtOAc and aq. 1M NaOH, and the layers were separated. The aq. layer was extracted with EtOAc. The combined org. extracts were washed with brine, dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the crude by FC (heptane/EtOAc 7/3) yielded the title compound (1.60 g, 65%) as an orange oil. LC-MS: tR=1.19 min, ES+: 654.33.

Workup

  1. customThe cooling bath was removed
  2. stirringthe reaction mixture was stirred for 1 h at rt
  3. stirringThe reaction mixture was stirred at rt for 2 h
  4. custompartitioned between EtOAc and aq. 1M NaOH
  5. customthe layers were separated
  6. extractionThe aq. layer was extracted with EtOAc
  7. washextracts were washed with brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. customthe solvents were removed under reduced pressure
  11. customPurification of the crude by FC (heptane/EtOAc 7/3)

Sources & evidence

ORD record
ord-601339b8c34f4cb5a49071a7ddfb7057
Source dataset
uspto-grants-2012_03
Patent number
US08138340B2

Reaction notes

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