Benzyl chloroformate → HCID 86601818, compound

HRID 2115909Notes

Reaction equation

HRID 2115909 reaction equation
[CH:1]1([C:6]2[C:14]3[O:13][CH:12]([CH2:15][NH2:16])[CH2:11][C:10]=3[CH:9]=[CH:8][CH:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(C(C)C)CC)(C)C.Cl[C:27]([O:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:28]>O1CCCC1>[CH2:30]([O:29][C:27](=[O:28])[NH:16][CH2:15][CH:12]1[CH2:11][C:10]2[CH:9]=[CH:8][CH:7]=[C:6]([CH:1]3[CH2:2][CH2:3][CH2:4][CH2:5]3)[C:14]=2[O:13]1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

Participants

5

Reactant 3

HCID 10387Benzyl chloroformateHCID 81531DiisopropylethylamineHCID 68961625HCID 68961625, compound

Product 1

HCID 86601818HCID 86601818, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of (7-cyclopentyl-2,3-dihydro-1-benzofuran-2-yl)methylamine (2.4 g, 9.46 mmol) in tetrahydrofuran (100 mL) cooled to 0° C. was added diisopropylethylamine (2.14 g, 16.58 mmol) followed by benzyl chloroformate (2.08 g, 12.19 mmol) and the reaction mixture was allowed to stir for 15 min. The reaction mixture was quenched with water (100 mL). The aqueous layer was extracted with ethyl acetate (2×200 mL) and the combined organic extracts were washed with saturated aqueous sodium chloride (100 mL), dried (magnesium sulfate) and the solvent removed in vacuo. Purification by flash column chromatography (silica, ethyl acetate:hexanes 1:9) provided 2.52 g (76%) of (±)-benzyl(7-cyclopentyl-2,3-dihydro-1-benzofuran-2-yl)methylcarbamate as a yellow oil. Rf=0.21 (silica, ethyl acetate:hexanes 2:8); Anal. calcd. for C22H25NO3 C, 75.19; H, 7.17; N, 3.99. Found C, 74.74; H, 7.02; N, 3.85. Chiral HPLC separation of (±)-benzyl(7-cyclopentyl-2,3-dihydro-1-benzofuran-2-yl)methylcarbamate (Chiralcel OJ, ethanol:hexane 1:1) provided two fractions. Fraction 1 (Rt=9.678 min, Chiralcel OJ, ethanol:hexane 1:1); Fraction 2 (Rt=12.824 min, Chiralcel OJ, ethanol:hexane 1:1).

Workup

  1. customThe reaction mixture was quenched with water (100 mL)
  2. extractionThe aqueous layer was extracted with ethyl acetate (2×200 mL)
  3. washthe combined organic extracts were washed with saturated aqueous sodium chloride (100 mL)
  4. dry with materialdried (magnesium sulfate)
  5. customthe solvent removed in vacuo
  6. customPurification by flash column chromatography (silica, ethyl acetate:hexanes 1:9)

Sources & evidence

ORD record
ord-d989e0afff914372a9c29bdf10327bf5
Source dataset
uspto-grants-2008_10
Patent number
US07435837B2

Reaction notes

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