Benzyl Alcohol → Benzyl 4-hydroxybicyclo[2.2.2]octan-1-ylcarbamate

HRID 2280742Notes

Reaction equation

[OH:1][C:2]12[CH2:9][CH2:8][C:5](C(O)=O)([CH2:6][CH2:7]1)[CH2:4][CH2:3]2.CC[N:15]([CH:19](C)C)C(C)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:29])C=CC=CC=1.[CH2:39]([OH:46])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>O1CCOCC1>[OH:1][C:2]12[CH2:3][CH2:4][C:5]([NH:15][C:19](=[O:29])[O:46][CH2:39][C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)([CH2:6][CH2:7]1)[CH2:8][CH2:9]2

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 4-hydroxybicyclo[2.2.2]octane-1-carboxylic acid (10.4 g, 61.1 mmol) in dioxane (150 mL) was added DIEA (11.8 g, 91.5 mmol), diphenyl phosphoryl azide (25 g, 91.5 mmol) and benzyl alcohol (131 g, 1.22 mol). The mixture was stirred at 80° C. overnight. Then the reaction was concentrated under reduce pressure to remove dioxane and benzyl alcohol (100° C., 2 mm Hg). The residue was purified by silica gel column chromatography (5% methanol in DCM) to give the title product (15.4 g, 54 mmol, yield 91%). 1H NMR (400 MHz, CDCl3) δ ppm 7.35-7.30 (m, 5H), 5.03 (s. 2H), 4.55 (br s, 1H), 2.01-1.95 (m, 6H), 1.77-1.72 (m, 6H; MS (ESI) m/z 276.3 [M+H]+.

Workup

concentrationThen the reaction was concentrated
customto remove dioxane and benzyl alcohol (100° C., 2 mm Hg)
customThe residue was purified by silica gel column chromatography (5% methanol in DCM)

Sources & evidence

ORD record: ord-4448654df0dd4c69b0971b682c29c078
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09139534B2

Reaction notes

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