Methyl p-toluenesulfonate → (+/-)-Benzyl (5-methoxy-2,3,6,7,8,9-hexahydro-6,9-ethanonaphtho[1,2-b]furan-2-yl)methylcarbamate

HRID 13969Notes

Reaction equation

HRID 13969 reaction equation
[CH3:1][O:2][C:3]1[C:17]2[CH:16]3[CH2:18][CH2:19][CH:13]([CH2:14][CH2:15]3)[C:12]=2[C:6]2[O:7][CH:8]([CH2:10][NH2:11])[CH2:9][C:5]=2[CH:4]=1.C(N(C(C)C)CC)(C)C.Cl[C:30]([O:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)=[O:31].CC1C=CC(S(OC)(=O)=O)=CC=1>>[CH3:1][O:2][C:3]1[C:17]2[CH:16]3[CH2:18][CH2:19][CH:13]([CH2:14][CH2:15]3)[C:12]=2[C:6]2[O:7][CH:8]([CH2:10][NH:11][C:30](=[O:31])[O:32][CH2:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[CH2:9][C:5]=2[CH:4]=1

Participants

5

Reactant 4

HCID 6645Methyl p-toluenesulfonateHCID 10387Benzyl chloroformateHCID 81531DiisopropylethylamineHCID 11334440(+/-)-1-(5-Methoxy-2,3,6,7,8,9-hexahydro-6,9-ethanonaphtho[1,2-b]furan-2-yl)methanamine

Product 1

HCID 86598576(+/-)-Benzyl (5-methoxy-2,3,6,7,8,9-hexahydro-6,9-ethanonaphtho[1,2-b]furan-2-yl)methylcarbamateYield 93%

Procedure

Treatment of (±)-1-(5-methoxy-2,3,6,7,8,9-hexahydro-6,9-ethanonaphtho[1,2-b]furan-2-yl)methanamine (2.5 g, 8.45 mmol) with diisopropylethylamine (2.73 g, 21.12 mmol) followed by benzyl chloroformate (1.73 g, 10.14 mmol) generally according to the procedure described for Intermediate 7 provided 3.08 g (93%) of (±)-benzyl (5-methoxy-2,3,6,7,8,9-hexahydro-6,9-ethanonaphtho[1,2-b]furan-2-yl)methylcarbamate as a colorless oil. Chiral HPLC separation of (±)-benzyl (5-methoxy-2,3,6,7,8,9-hexahydro-6,9-ethanonaphtho[1,2-b]furan-2-yl)methylcarbamate (Chiralcel OJ, methanol) provided two fractions. Fraction 1 (Rt=13.252 min, Chiralcel OJ, methanol); Fraction 2 (Rt=18.196 min, Chiralcel OJ, methanol). Treatment of 0.460 g of fraction 1 obtained from the chiral HPLC separation of (±)-benzyl (5-methoxy-2,3,6,7,8,9-hexahydro-6,9-ethanonaphtho[1,2-b]furan-2-yl)methylcarbamate (Chiralcel OJ, methanol) with palladium on carbon (10 wt. %, 0.05 g) generally according to the procedure described for Example 2 provided 0.304 g (88%) of (+)-1-(5-methoxy-2,3,6,7,8,9-hexahydro-6,9-ethanonaphtho[1,2-b]furan-2-yl)methanamine as a white solid, hydrochloride salt. [α]D5=+40.03 (c 9.99 in methanol); mp>220° C.; Anal. calcd. for C16H21NO2HCl: C, 64.97; H, 7.5; N, 4.74. Found: C, 64.62; H, 7.79; N, 4.54.

Sources & evidence

ORD record
ord-b66fe878a72f4f048758a9443b8201b8
Source dataset
uspto-grants-2010_06
Patent number
US07728155B2

Reaction notes

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