Benzyl chloroformate → ((S)-5-bromo-indan-2-yl)-carbamic acid benzyl ester

HRID 658342Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH2:7][C@H:6]([NH2:11])[CH2:5]2.Cl[C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:14]>ClCCl>[CH2:16]([O:15][C:13](=[O:14])[NH:11][C@@H:6]1[CH2:5][C:4]2[C:8](=[CH:9][CH:10]=[C:2]([Br:1])[CH:3]=2)[CH2:7]1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

Conditions

Temperature: 0 °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

filtrationThe solution is filtered

Sources & evidence

ORD record: ord-367249be1bf344958694d3368bf11ac7
Source dataset: uspto-grants-2011_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08076489B2

Reaction notes

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