Benzyl chloroformate → HCID 86598542, compound

HRID 13916Notes

Reaction equation

HRID 13916 reaction equation
[O:1]1[CH:5]([CH2:6][NH2:7])[CH2:4][C:3]2[CH:8]=[CH:9][C:10]3[CH2:11][CH2:12][CH2:13][C:14]=3[C:2]1=2.C(N(C(C)C)CC)(C)C.Cl[C:25]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26]>O1CCCC1>[O:1]1[CH:5]([CH2:6][NH:7][C:25](=[O:26])[O:27][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:4][C:3]2[CH:8]=[CH:9][C:10]3[CH2:11][CH2:12][CH2:13][C:14]=3[C:2]1=2

Participants

5

Reactant 3

HCID 10387Benzyl chloroformateHCID 81531DiisopropylethylamineHCID 11480921HCID 11480921, compound

Product 1

HCID 86598542HCID 86598542, compoundYield 68.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (±)-1-(3,6,7,8-tetrahydro-2H-indeno[4,5-b]furan-2-yl)methanamine (0.568 g, 3.00 mmol) in tetrahydrofuran (30 mL) cooled to 0° C. was added diisopropylethylamine (0.427 g, 3.30 mmol) followed by benzyl chloroformate (0.538 g, 3.15 mmol) and the reaction mixture was allowed to stir at 0° C. for 1 h. The reaction mixture was quenched by the addition of saturated aqueous ammonium chloride (100 mL) and extracted with diethyl ether (2×150 mL). The combined organic extracts were washed with saturated aqueous sodium chloride (100 mL), dried (magnesium sulfate), and the solvent was removed in vacuo to provide a crude oil. Purification by flash column chromatography (silica, ethyl acetate:hexanes 1:9) afforded 0.663 g (68%) of (±)-benzyl 3,6,7,8-tetrahydro-2H-indeno[4,5-b]furan-2-ylmethylcarbamate as a white solid. Rf=0.30 (silica, ethyl acetate:hexanes 1:9); mp 99-101° C.; Anal. calcd. for C20H21NO3: C, 74.28; H, 6.55; N, 4.33. Found: C, 73.82; H, 6.53; N, 4.25. Chiral HPLC separation of (±)-benzyl 3,6,7,8-tetrahydro-2H-indeno[4,5-b]furan-2-ylmethylcarbamate (Chiralcel OJ, isopropanol:hexane 7:3) provided two fractions. Fraction 1 (Rt=13.237 min, Chiralcel OJ, isopropanol:hexanes 3:7); Fraction 2 (Rt=16.526 min, Chiralcel OJ, isopropanol:hexanes 3:7).

Workup

  1. customThe reaction mixture was quenched by the addition of saturated aqueous ammonium chloride (100 mL)
  2. extractionextracted with diethyl ether (2×150 mL)
  3. washThe combined organic extracts were washed with saturated aqueous sodium chloride (100 mL)
  4. dry with materialdried (magnesium sulfate)
  5. customthe solvent was removed in vacuo
  6. customto provide a crude oil
  7. customPurification by flash column chromatography (silica, ethyl acetate:hexanes 1:9)

Sources & evidence

ORD record
ord-0291e99f891346d290ef45f1279645bd
Source dataset
uspto-grants-2010_06
Patent number
US07728155B2

Reaction notes

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