Benzyl chloroformate → benzyl [(2R)-6-iodo-3,4-dihydro-2H-chromen-2-yl]methylcarbamate

HRID 896857Notes

Reaction equation

HRID 896857 reaction equation
Cl.[I:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[O:9][C@@H:8]([CH2:13][NH2:14])[CH2:7][CH2:6]2.[CH2:15]([O:22][C:23](Cl)=[O:24])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[OH-].[Na+]>O1CCCC1>[I:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[O:9][C@@H:8]([CH2:13][NH:14][C:23](=[O:24])[O:22][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:7][CH2:6]2

Participants

5

Reactant 3

HCID 10387Benzyl chloroformateHCID 14798Sodium HydroxideHCID 69642398HCID 69642398, compound

Product 1

HCID 10159298benzyl [(2R)-6-iodo-3,4-dihydro-2H-chromen-2-yl]methylcarbamateYield 99.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of (R)-6-iodo-chroman-2-methylamine hydrochloride of Example 10 (3.3 g, 10 mmol) and benzylchloroformate (1.57 mL, 11 mmol) in tetrahydrofuran (30 mL) cooled in an ice-water bath was added slowly 1N aqueous sodium hydroxide in 20 minutes. The resulting mixture was stirred for 1 hour. The organic layer was separated and concentrated in vacuo. The aqueous layer was extracted with ethyl acetate (50 mL×2). The combined ethyl acetate layer was combined with the above residue and washed with water (50 mL), brine (50 mL), and dried over anhydrous sodium sulfate. Removal of the solvent in vacuo afforded the crude product as a white solid (4.2 g, 99%). 1H nmr (DMSO d6) δ 1.5-1.6 (m, 2H), 1.9 2.0 (m, 1H), 2.7 (m, 2H), 3.3 (m, 2H), 4.0 (m, 1H), 5.0 (s, 2H), 6.5 (d, 1H), 7.3 (m, 7H), 7.5 (t, 1H).

Workup

  1. temperaturecooled in an ice-water bath
  2. customThe organic layer was separated
  3. concentrationconcentrated in vacuo
  4. extractionThe aqueous layer was extracted with ethyl acetate (50 mL×2)
  5. washwashed with water (50 mL), brine (50 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. customRemoval of the solvent in vacuo

Sources & evidence

ORD record
ord-7fd06caf395b4a31923cc679c327290e
Source dataset
uspto-grants-2005_07
Patent number
US06919371B2

Reaction notes

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