Diisopropylethylamine → (2S,5R)-6-(allyloxy)-2-((tert-butyldimethylsilyloxy)methyl)-4-methyl-1,6-diazabicyclo[3.2.1]oct-3-en-7-one

HRID 627079Notes

Reaction equation

HRID 627079 reaction equation
[CH2:1]([O:4][NH:5][C@@H:6]1[C:11]([CH3:12])=[CH:10][C@@H:9]([CH2:13][O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])[NH:8][CH2:7]1)[CH:2]=[CH2:3].C(N(CC)C(C)C)(C)C.Cl[C:32](Cl)([O:34]C(=O)OC(Cl)(Cl)Cl)Cl>C(#N)C>[CH2:1]([O:4][N:5]1[C:32](=[O:34])[N:8]2[CH2:7][C@H:6]1[C:11]([CH3:12])=[CH:10][C@H:9]2[CH2:13][O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:16])[CH3:17])[CH:2]=[CH2:3]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 94429Triphosgene2×HCID 131735277(3R,6S)-6-{[(tert-butyldimethylsilyl)oxy]methyl}-4-methyl-N-(prop-2-en-1-yloxy)-1,2,3,6-tetrahydropyridin-3-amine2×

Product 1

HCID 89852160(2S,5R)-6-(allyloxy)-2-((tert-butyldimethylsilyloxy)methyl)-4-methyl-1,6-diazabicyclo[3.2.1]oct-3-en-7-oneYield 228.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

To a solution of O-allyl-N-((3R,6S)-6-((tert-butyldimethylsilyloxy)methyl)-4-methyl-1,2,3,6-tetrahydropyridin-3-yl)hydroxylamine (Intermediate 12, 2 g, 6.40 mmol) and N,N-diisopropylethylamine (4.46 mL, 25.60 mmol) in acetonitrile (555 mL) at 0° C. was added triphosgene (0.760 g, 2.56 mmol) as a solution in acetonitrile (45 mL). The triphosgene solution was added via syringe pump at a rate of 0.1 mL/min. Once addition was complete the reaction was stirred at room temperature overnight. The reaction mixture was concentrated to dryness, diluted with ethyl acetate, washed with water and brine, dried over magnesium sulfate, filtered and concentrated. The aqueous washes were found to contain some product and were extracted twice with ethyl acetate. The combined organics were dried over magnesium sulfate, filtered and combined with previous extracts. Silica gel chromatography (0%-20% ethyl acetate/hexanes) afforded the desired product (1.980 g, 91%) as a light orange oil.

Workup

  1. additionOnce addition
  2. concentrationThe reaction mixture was concentrated to dryness
  3. additiondiluted with ethyl acetate
  4. washwashed with water and brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. extractionwere extracted twice with ethyl acetate
  9. dry with materialThe combined organics were dried over magnesium sulfate
  10. filtrationfiltered

Sources & evidence

ORD record
ord-451c8d0eb6024c878b67f059d082082a
Source dataset
uspto-grants-2016_04
Patent number
US09309245B2

Reaction notes

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