Benzyl chloroformate → HCID 73991019, compound

HRID 2414836Notes

Reaction equation

HRID 2414836 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([O:11][CH2:12][C@@H:13]2[O:18][C:17]3[C:19]([CH:24]=[CH:25][CH3:26])=[C:20]([NH2:23])[CH:21]=[CH:22][C:16]=3[O:15][CH2:14]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.Cl[C:28]([O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:29].C(N(CC)C(C)C)(C)C>C(OCC)(=O)C>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([O:11][CH2:12][CH:13]2[O:18][C:17]3[C:19]([CH:24]=[CH:25][CH3:26])=[C:20]([NH:23][C:28]([O:30][CH2:31][C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)=[O:29])[CH:21]=[CH:22][C:16]=3[O:15][CH2:14]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 10387Benzyl chloroformateHCID 81531DiisopropylethylamineHCID 86586603HCID 86586603, compound

Product 1

HCID 73991019HCID 73991019, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of {(2R)-7-amino-8-[1-propenyl]-2,3-dihydro-1,4-benzodioxin-2-yl}methyl 4-methylbenzenesulfonate (4.20 g, 11.2 mmole) in ethyl acetate (150 mL) was added benzyl chloroformate (8.00 mL, 56.0 mmole). The reaction mixture was stirred under nitrogen for 0.5 hour, then a solution of N,N-diisopropylethylamine (9.75 mL, 56 mmole) in ethyl acetate (75 mL) was added dropwise over a period of 0.5 hour. The mixture was stirred at room temperature under nitrogen overnight. The reaction was diluted in volume to 350 ml and was then washed with 2N HCl (2×100 mL), saturated sodium bicarbonate (150 mL) and brine (100 mL), dried over magnesium sulfate, filtered and evaporated to an oil. The crude oil was column chromatographed on silica gel with 10% ethyl acetate/hexane to remove impurities and the product eluted with 60% ethyl acetate/hexane to give the (R)-enantiomer of the title compound as a yellow oil (4.5 g, 79%). 1H (CDCl3) doublet 7.8 δ (2); multiplet 7.4 δ (7 H); doublet 6.7 δ (2 H); multiplet 6.0-6.2 δ (2 H); singlet 5.2 δ (2 H); multiplet 4.4 δ (1 H); multiplet 4.2 δ (3H); multiplet 4.0 δ (1 H); singlet 2.4 δ (3 H); doublet 1.9 δ (3 H).

Workup

  1. stirringThe mixture was stirred at room temperature under nitrogen overnight
  2. additionThe reaction was diluted in volume to 350 ml
  3. washwas then washed with 2N HCl (2×100 mL), saturated sodium bicarbonate (150 mL) and brine (100 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated to an oil
  7. customchromatographed on silica gel with 10% ethyl acetate/hexane
  8. customto remove impurities
  9. washthe product eluted with 60% ethyl acetate/hexane

Sources & evidence

ORD record
ord-b0c1da6a8f894d7da8530d6934473bd0
Source dataset
uspto-grants-2004_11
Patent number
US06815448B2

Reaction notes

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