Chlorotriethylsilane → Iminodicarbonsaure

HRID 596018Notes

Reaction equation

HRID 596018 reaction equation
[C:1]([NH:4][C:5]([OH:7])=[O:6])([OH:3])=[O:2].[C:8]([O:12][C:13]([NH:15][C:16]1[C:17]([C:29]2[CH:37]=[CH:36][C:32]([C:33]([O-:35])=[O:34])=[C:31]([F:38])[CH:30]=2)=[N:18][C:19]([CH:22]2[CH2:27][CH2:26][C:25](=[O:28])[CH2:24][CH2:23]2)=[CH:20][N:21]=1)=[O:14])([CH3:11])([CH3:10])[CH3:9].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH2:49]([Si:51]([CH2:55][CH3:56])([CH2:53][CH3:54])Cl)[CH3:50].C(=O)(O)[O-].[Na+]>C1COCC1>[C:1]([NH:4][C:5]([OH:7])=[O:6])([OH:3])=[O:2].[C:8]([O:12][C:13]([NH:15][C:16]1[C:17]([C:29]2[CH:37]=[CH:36][C:32]([C:33]([O-:35])=[O:34])=[C:31]([F:38])[CH:30]=2)=[N:18][C:19]([CH:22]2[CH2:23][CH2:24][C:25]([O:28][Si:51]([CH2:55][CH3:56])([CH2:53][CH3:54])[CH2:49][CH3:50])=[CH:26][CH2:27]2)=[CH:20][N:21]=1)=[O:14])([CH3:11])([CH3:9])[CH3:10]

Participants

8

Reactant 5

HCID 13819ChlorotriethylsilaneHCID 516892Sodium BicarbonateHCID 2733832Lithium HexamethyldisilazideHCID 13267551IminodicarbonsaureHCID 1317346144-(3-((Tert-butoxycarbonyl)amino)-6-(4-oxocyclohexyl)pyrazin-2-yl)-2-fluorobenzoate

Product 2

HCID 13267551IminodicarbonsaureHCID 1317346154-(3-((Tert-butoxycarbonyl)amino)-6-(4-((triethylsilyl)oxy)cyclohex-3-en-1-yl)pyrazin-2-yl)-2-fluorobenzoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of imidodicarbonic acid, 4-(3-((tert-butoxycarbonyl)amino)-6-(4-oxocyclohexyl)pyrazin-2-yl)-2-fluorobenzoate, 1,3-bis(1,1-dimethylethyl) ester (12.1 g, 20.66 mmol) in THF (68.9 mL) was slowly added LiHMDS (1 M in THF) (22.73 mL, 22.73 mmol) at −78° C. After stirring for 30 min, triethylchlorosilane (3.67 mL, 21.69 mmol) was added. The reaction mixture was warmed to room temperature and stirred for 1 h. Saturated sodium bicarbonate solution was added, and the mixture was extracted with EtOAc. The organic layer was washed well with water and brine, dried over anhydrous NaHCO3, filtered off, and concentrated in vacuo. The crude product was purified by flash chromatography eluting with 5% of EtOAc/heptane to provide imidodicarbonic acid, 4-(3-((tert-butoxycarbonyl)amino)-6-(4-((triethylsilyl)oxy)cyclohex-3-en-1-yl)pyrazin-2-yl)-2-fluorobenzoate, 1,3-bis(1,1-dimethylethyl) ester (12.1 g, 17.29 mmol). LCMS (m/z, neutral-nonpolar method): 701.8 (MH+), 1.14 min; 1H NMR (400 MHz, CDCl3) δ ppm 8.41 (s, 1H), 8.00-7.88 (m, 1H), 7.57-7.46 (m, 2H), 4.97 (br. s., 1H), 3.16-3.00 (m, 1H), 2.49-2.38 (m, 2H), 2.38-2.23 (m, 1H), 2.19-1.94 (m, 3H), 1.61 (s, 9H), 1.33 (s, 18H), 1.06-0.94 (m, 8H), 0.77-0.64 (m, 6H).

Workup

  1. customat −78° C
  2. stirringstirred for 1 h
  3. extractionthe mixture was extracted with EtOAc
  4. washThe organic layer was washed well with water and brine
  5. dry with materialdried over anhydrous NaHCO3
  6. filtrationfiltered off
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by flash chromatography
  9. washeluting with 5% of EtOAc/heptane

Sources & evidence

ORD record
ord-c675621d987c4996999d772cc50dacdb
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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