BOC-3-AMINOBENZYLALCOHOL

A mixture of 3-aminobenzyl alcohol (1.365 g, 11.08 mmol) in dry tetrahydrofuran (15 mL ) was treated at 23 To a solution (3-aminophenyl)methanol(88.5 g, 719 mmol)in THF(80 mL)was added ditert-butyl dicarbonate(184 mL, 790 mmol). The mixture was stirred at 25 °C overnight. The mixture wasthen concentrated to dryness and the residue was purified by silica gel column chromatography(elutedwith Et0ac/hexanes=l:9, v/v)to afford the title compound(161.1 g, 722 mmol, 100percent yield), as a whitesolid. LCMS(Methodj, Table 7)R1=1.77 min; MS m/z = 246 [M+Na+].Step 2: Synthesis oftert-butyl (3-(bromomethyl)phenyl)carbamate(3-Amino-phenyl)-methanol (850 mg, 6.90 mmol) was suspended in tetrahydrofuran (8 mL) and di-tert-butyl dicarbonate (1.58 g, 7.25 mmol) was added. The solids quickly dissolved with stirring and the resulting solution was heated to 80° C. for 5 h and then at 25° C. for 16 h. The solution was concentrated in vacuo to give a thick yellow oil. Purification by ISCO flash column chromatography (Teledyne Isco RediSep Flash Column 120 g; 5percent ethyl acetate/hexanes to 75percent ethyl acetate/hexanes) afforded (3-hydroxymethyl-phenyl)-carbamic acid tert-butyl ester (1.67 g, >100percent) as a clear oil: H(3-Amino-phenyl)-methanol (11) (RExample 72N-hydroxy-2-[3-(isobutyrylamino)benzyl]-1-oxo-1, 2-dihydroisoquinoline-7-carboxamide; Compound I-174 Step 1: tert-butyl [3-(hydroxymethyl)phenyl]carbamateTo a solution of (3-aminophenyl)methanol (0.50 g, 4.06 mmol) dissolved in tetrahydrofuran (15 mL) was added di-tert-butyl dicarbonate (0.97 g, 4.5 mmol). The reaction mixture was stirred at rt overnight. The mixture was then concentrated to dryness and the residue was purified by flash silica gel chromatography (0percent to 50percent EtOAc/hexanes) to afford tert-butyl [3-(hydroxymethyl)phenyl]carbamate (0.90 g, 99percent). LC-MS: (FA) ES+150.Into a 250-mi. round-bottom flask, was placed a solution of (3-aminophenyl)methanol (5 g, 40.60 mmol, 1.00 equiv) and di-tert-butyl dicarbonate (9.60 g, 43.99 mmol, 1.08 equiv) in tetrahydrofuran (150 mL). The resulting solution was stirred overnight at room temperature. Theresulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:10) to yield 8.92 g (98percent) of tert-butyl N-[3- (hydroxymethyl)phenyl]carbamate as a white solid.Into a 250-mL round-bottom flask, was placed a solution of (3-aminophenyl)methanol (5 g, 40.60 mmol, 1.00 equiv) and di-tert-butyl dicarbonate (9.60 g, 43.99 mmol, 1.08 equiv) in tetrahydrofuran (150 mL). The resulting solution was stirred overnight at room temperature. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1 : 10) to yield 8.92 g (98percent) of tert-butyl N-[3- (hydroxymethyl)phenyl]carbamate as a white solid.3). SYNTHETIC PREPARATION 3. A solution of (3-aminophenyl)methanol (10) (1.0 g, 8.1 mmol), (Boc)Compound 14A: tert—butyl (3—(hydroxymethyl)phenyl) carbamate (3—aminophenyl)methanol (3 g, 24.36 mmol, 1.00 equiv) was dissolved in THF(60 mL) after which di—tert—butyl dicarbonate (6.38 g, 29.23 mmol, 1.20 equiv) wasthen added. The reaction mixture was left under agitation overnight at ambient temperature and the reaction was then diluted by adding 200 mL of water. The product was extracted 3 times with 100 mL of AcOEt and the organic phases were then recombined, dried over sodium sulfate, filtered and concentrated under reduced pressureto yield the crude product (13.85 g of compound 14A) in the form of a yellow oil.EXAMPLE 3 EXAMPLE 118 To solution of ethyl 3- [(tert-butoxycarbonyl)amino]benzoate (14 g, 0.052 mol) in tetrahydrofuran (70 ml) was added slowly to a solution of lithium aluminium hydride (2 g, 0.052 mol) in tetrahydrofuran (70 ml) at 0°C. The reaction mixture was allowed to warm to room temperature and stirred for 1 hour. The reaction mixture was quenched with a saturated aqueous solution of sodium sulfate. The resulting mixture was filtered through celite bed and the residue washed with fresh tetrahydrofuran (30 ml). The solvent from the combined filtrate was evaporated under reduced pressure to obtain 9 g of the titled product as white solid in 78percent yield.

Molecular Weight:223.27
XLogP3:2
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:235
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes