benzyl N-(5-bromo-2,3-dihydro-1H-inden-2-yl)carbamate → Isohexane ethyl acetate

HRID 658343Notes

Reaction equation

HRID 658343 reaction equation
[Br-].[CH2:2]([Zn+])[CH:3]([CH3:5])[CH3:4].[CH2:7]([O:14][C:15](=[O:27])[NH:16][CH:17]1[CH2:25][C:24]2[C:19](=[CH:20][CH:21]=[C:22](Br)[CH:23]=2)[CH2:18]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>C1COCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:7]([O:14][C:15](=[O:27])[NH:16][C@@H:17]1[CH2:25][C:24]2[C:19](=[CH:20][CH:21]=[C:22]([CH2:2][CH:3]([CH3:5])[CH3:4])[CH:23]=2)[CH2:18]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[C:15]([O:14][CH2:7][CH3:8])(=[O:27])[CH3:2].[CH3:11][CH2:10][CH2:9][CH:8]([CH3:13])[CH3:7]

Participants

6

Reactant 2

HCID 59464189benzyl N-(5-bromo-2,3-dihydro-1H-inden-2-yl)carbamateHCID 178448254HCID 178448254, compound

Product 2

HCID 21882781Isohexane ethyl acetateHCID 66744187(S)-(5-Isobutyl-indan-2-yl)-carbamic acid benzyl ester

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

(S)-5-Bromo-indan-2-ylamine (1.0 g) suspended in dichloromethane (10 ml) is cooled to 0° C. and benzyl chloroformate (0.74 ml) is added dropwise and the reaction mixture is stirred for 0.5 hour. The solution is filtered to give (S)-(5-Bromo-indan-2-yl)-carbamic acid benzyl ester. PdCl2(dppf)2 (59 mg) is placed in a dry flask under argon and isobutyl zinc bromide (50 ml, 0.5 M solution in THF) is added. (5-Bromo-indan-2-yl)-carbamic acid benzyl ester (2.50 g) is dissolved in dry THF (2 ml) and the solution is added to the reaction mixture. The reaction mixture is stirred at 50° C. for 18 hours then quenched with HCl(aq) (2M) and partitioned between ethyl acetate and water. The organic layer is dried over MgSO4, filtered and the solvent removed in vacuo. The title compound is obtained by flash column chromatography (silica, eluent ethyl acetate/iso-hexane 1:4). 1H nmr (CDCl3, 400 MHz); 7.35 (m, 5H), 7.10 (d, 1H), 7.00 (s, 1H), 6.90 (d, 1H), 5.1 (s, 2H), 4.55 (m, 1H), 3.30 (m, 2H), 2.75 (dt, 2H), 2.45 (d, 2H), 1.80 (m, 1H), 0.90 (d, 6H).

Workup

  1. additionthe solution is added to the reaction mixture
  2. customthen quenched with HCl(aq) (2M)
  3. custompartitioned between ethyl acetate and water
  4. dry with materialThe organic layer is dried over MgSO4
  5. filtrationfiltered
  6. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-972264d24c0940439c70e26c478b902a
Source dataset
uspto-grants-2011_12
Patent number
US08076489B2

Reaction notes

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