Benzyl chloroformate → HCID 73991019, compound

HRID 130389Notes

Reaction equation

HRID 130389 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-benzo-dioxin-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 (7H); doublet 6.7 δ (2H); multiplet 6.0-6.2 δ (2H); singlet 5.2 δ (2H); multiplet 4.4 δ (1H); multiplet 4.2 δ (3H); multiplet 4.0 δ (1H); singlet 2.4 δ (3H); doublet 1.9 δ (3H).

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-572249394fb840c28f52c5c1e757cb33
Source dataset
uspto-grants-2008_06
Patent number
US07381723B2

Reaction notes

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