BOC-4-AMINOBENZYLALCOHOL

To a solution of p-amino-benzylalcohol (1 g, 8.12 mmol, 1 eq) in 80 mL of anhydrous THF were added DIEA (1.4 mL, 8.12 mmol, 1 eq) and BoCTo a 250 mL round bottom flask was added (4-amino-phenyl)-methanol (4.13 g, 33.6 mmol), dichloromethane (50 mL) followed by di-tert-butyl dicarbonate (8.5 g, 36.9 mmol). The mixture was allowed to stir for 18 h under a nitrogen atmosphere. By TLC, a small amount of starting amine remained, which reacted during concentration by rotary evaporation. The product was purified by column chromatography (ethyl acetate : hexanes, 1:1) to yield (4- hydroxymethyl-phenyl)-carbamic acid tert-butyl ester (7.36 g, 33.0 mmol, 98 percent) as a white solid.General procedure: The reactions were carried out in a 50 mL RB flask under reduced pressure for 10 min at 80°C unless reported differently. In a typical experiment, 5 mmol of amine was added to 5 mmol of BOC anhydride, and the reaction was allowed to proceed for 10 min. The desired product was obtained in a rotary evaporator under vacuum conditions.PREPARATION 15; Preparationof teri-buty\ 4-(chloromethyl)phenylcarbamate; A. To a stirred solution of 4-aminobenzyl alcohol ( 1.50 g. 12.18 mmol) in 1.4-dioxane (30 mL) was added sodium hydroxide (0.49 g. 12.2 mmol) in water (30 mL). The mixture was cooled to 0 A i00-mL, three-necked, round-bottomed flask, was equipped with a magnetic stimng bar, a retlux condenser, and a pressure-equalizing dropping funnel that was connected to a nitrogen flow line and charged with a solution of 97percent di-tert-butyl dicarbonate (4.04 g, 18.5 nimol) in tetralydrofuran (30 mid). Amino benzyi alcohol (2.5 g, 20.3 mmol) was placed in the flask and suspended in tetrahydrofuran (65 mL) and 99percent triethylamine (3.1 mL, 22 mmoi). The resultmg white suspension was cooled with an ice-water bath and the solution of di-tert-butyl dicarbonate was added dropwise over a period of 30 minutes. After 10 mm of additional stirring, the ice-water bath was removed and the suspension was stirred overnight at room temperature, then warmed at 50°C for a further 3 hours. T he solvent was removed tinder reduced pressure and the residue partitioned between EtOAc (50 mL) and saturated aqueous bicarbonate solution (50 mL). The aqueous phase was extracted with three 50-ni. portions of EtOAc. The combined organic phases were dried with anhydrous MgSO4 and concentrated under reduced pressure to give 3.72 g (83percent yield) of the product as a brown oil that was used without further purification. ‘H NMR (as rotamers) (400 MHz, CDCh) 6 9.26 (s, I H), 8.64 (s, iH), 7.39 (.4H), 7.20 (4H), 5, 75 (s, 1H), 5.05 (2H), 4.49 —4.35 (m, 4H), i.47 (s, 9H), 1.40 (s, 1H).Intermediate 10: tert-butyl 4-(hydroxymethyl)phenylcarbamateTo a solution of p-aminobenzyl alcohol (38, 2 mmol) in 100 ml dioxane were added triethylamine (114 mmol) and di-tert-butyldicarbonate (42, 0 mmol) was added in portions. The mixture was stirred overnight at room temperature. The solvent was evaporated. EtOAc was added and washed with 2N HCI, saturated NaHCO3 and brine solution. The organic layer was dried over Na2SO4 and evaporated to yield a brown oil.Yield: 82 percent, MS (ESI) m/z 224.3 [M+H]1H-NMR (ODd3, 400 MHz) 51.54 (s, 9H), 4.65 (s, 2H), 6.54 (s, 1H), 7.22-7.43 (m, 4H).tert-Butyl (4-(hydroxymethyl)phenyl)carbamate 19. To a solution of ra-aminobenzyl alcohol (0.123 g, 0.0999 mmol) in AcOH (10percent in water, 8 mL) was added a solution of di-feri-butyl dicarbonate in THF (1 M, 1.05 mL, 1 .05 mmol), and the reaction was stirred for 18 h at ambient temperature. Water (30 mL) was added, and the mixture was basified with a NaOH solution (2 M) to pH 14. The resulting mixture was extracted with EtTo a solution of (4-aminophenyl)methanol (30, 8.0 g, 65.0 mmol) in THF (50 mL) were added Boc

Molecular Weight:223.27
XLogP3:1.6
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:4
Exact Mass:223.12084340
Monoisotopic Mass:223.12084340
Topological Polar Surface Area:58.6
Heavy Atom Count:16
Complexity:227
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes