Benzyl chloroformate → (+)-Benzyl[7-(4-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methylcarbamate

HRID 2115975Notes

Reaction equation

[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[O:15][CH:14]([CH2:17][NH2:18])[CH2:13][C:12]=3[CH:11]=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.Cl[C:29]([O:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)=[O:30]>>[CH2:32]([O:31][C:29](=[O:30])[NH:18][CH2:17][CH:14]1[CH2:13][C:12]2[CH:11]=[CH:10][CH:9]=[C:8]([C:5]3[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][CH:6]=3)[C:16]=2[O:15]1)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

Reactant 3

HCID 10387Benzyl chloroformate

HCID 81531Diisopropylethylamine

HCID 11960864(+/-)-[7-(4-Methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine

Product 1

HCID 86599135(+)-Benzyl[7-(4-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methylcarbamateYield 93%

Procedure

Treatment of (±)-[7-(4-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine (0.385 g, 1.396 mmol) with diisopropylethylamine (0.270 g, 2.09 mmol) and benzyl chloroformate (0.285 g, 1.675 mmol) generally according to the procedure described for Intermediate 12 provided 0.483 g (93%) of (±)-benzyl[7-(4-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methylcarbamate as colorless oil. Rf=0.47 (silica, ethyl acetate:hexane 2:8); mp 83-86° C.; Anal. calcd. for C24H23NO3: C, 77.19; H, 6.21; N, 3.75. Found: C, 76.97; H, 5.99; N, 3.68. Chiral HPLC separation of (±)-benzyl[7-(4-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methylcarbamate (Chiralpak OD, methanol:carbon dioxide 1:1) provided two fractions. Fraction 1 (Rt=3.788 min Chiralpak OD, methanol:carbon dioxide 1:1); Fraction 2 (Rt=4.398 min, Chiralpak OD, methanol:carbon dioxide 1:1).

Sources & evidence

ORD record: ord-23168e2d7f654953b87986a2045873f4
Source dataset: uspto-grants-2008_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07435837B2

Reaction notes

Loading…