Benzyl chloroformate → (R)-benzyl 5-bromo-2,3-dihydro-1H-inden-2-ylcarbamate

HRID 42990Notes

Reaction equation

HRID 42990 reaction equation
CC1(C)[C@@H]2CC[C@@]1(CS(O)(=O)=O)C(=O)C2.[Br:16][C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[CH2:22][C@@H:21]([NH2:26])[CH2:20]2.C(=O)([O-])[O-].[K+].[K+].Cl[C:34]([O:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)=[O:35]>CCOC(C)=O.O>[Br:16][C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[CH2:22][C@@H:21]([NH:26][C:34](=[O:35])[O:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[CH2:20]2

Participants

6

Reactant 3

HCID 10387Benzyl chloroformateHCID 11430Potassium CarbonateHCID 46899975(R)-5-Bromo-2-aminoindan(1S)-(+)-10-camphorsulfonate

Product 1

HCID 70241379(R)-benzyl 5-bromo-2,3-dihydro-1H-inden-2-ylcarbamateYield 89.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent2×

Procedure

(R)-5-bromo-2,3-dihydro-1H-inden-2-amine((1S,4R)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptan-1-yl)methanesulfonate (12.56 mmol, 5.58 g) was dissolved in EtOAc (30 mL)/water (30 mL) and potassium carbonate (37.7 mmol, 5.21 g) added. The mixture was cooled in an ice bath and benzyl chloroformate (13.81 mmol, 1.964 mL, 2.356 g) added dropwise. Stirring was continued overnight during which time the reaction came to room temperature. The crude reaction mixture was diluted with water and ethylacetate and the phases mixed and separated. The aqueous layer was further extracted with EtOAc (×2). Combined organics were dried and concentrated before crystallisation of the product from ethylacetate/heptane mixture to give (R)-benzyl 5-bromo-2,3-dihydro-1H-inden-2-ylcarbamate as colourless needles (3.89 g, 89%). 1H NMR (400 MHz, CDCl3) δ 2.79 (m, 2H) 3.26 (m, 2H) 4.53 (bm, 1H) 4.93 (bm, 1H) 5.10 (bs, 2H) 7.07 (m, 1H) 7.26-7.37 (m, 7H)

Workup

  1. additionadded
  2. temperatureThe mixture was cooled in an ice bath
  3. customcame to room temperature
  4. customThe crude reaction mixture
  5. additionthe phases mixed
  6. customseparated
  7. extractionThe aqueous layer was further extracted with EtOAc (×2)
  8. customCombined organics were dried
  9. concentrationconcentrated before crystallisation of the product from ethylacetate/heptane mixture

Sources & evidence

ORD record
ord-38428abe86d144098864d4889cd78773
Source dataset
uspto-grants-2013_09
Patent number
US08536214B2

Reaction notes

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