N-benzyl-1-(4-methoxyphenyl)propan-2-amine

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A sample of 3.36 g (13.2 mmol) of the racemate 1-(4′-methoxyphenyl)-2-benzylaminopropane (42) was reacted with 2.0 g (13.2 mmol) of (R)-(−)-mandelic acid to give 740 mg (44% based on enantiomeric abundance) of the free amine after workup. 1H NMR, (CDCl3) δ□ 1.10 (d, 3H, J=6.2 Hz), 2.55-2.76 (m, 2H), 2.88-2.95 (m, 1H), 3.73-3.88 (m, 2H), 3.79 (s, 3H), 6.80 (d, 2H, J=8.7 Hz), 7.08 (d, 2H, J=8.4 Hz), 7.15-7.30 (m, 5H); MS (APCI+) m/z (rel): 256 (100); [α]D=+30.5° (c=1.1 MeOH).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A sample of 3.36 g (13.2 mmol) of the racemate 1-(4′-methoxyphenyl)-2-benzylaminopropane (42) was reacted with 2.0 g (13.2 mmol) of (R)-(−)-mandelic acid to give 740 mg (44% based on enantiomeric abundance) of the free amine after workup. 1H NMR, (CDCl3) δ□ 1.10 (d, 3H, J=6.2 Hz), 2.55-2.76 (m, 2H), 2.88-2.95 (m, 1H), 3.73-3.88 (m, 2H), 3.79 (s, 3H), 6.80 (d, 2H, J=8.7 Hz), 7.08 (d, 2H, J=8.4 Hz), 7.15-7.30 (m, 5H); MS (APCI+) m/z (rel): 256 (100); [α]D=+30.5° (c=1.1 MeOH).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A sample of 3.02 g (11.8 mmol) of 1-(4′-methoxyphenyl)-2-benzylaminopropane (42) was reacted with 1.8 g (11.8 mmol) (S)-(+)-mandelic acid to give 530 mg (35% based on enantiomeric abundance) of the free amine after workup. 1H NMR (CDCl3) δ□ 1.10 (d, 3H, J=6.3 Hz), 2.57-2.76 (m, 2H), 2.88-2.94 (m, 1H), 3.79 (s, 3H), 3.72-3.88 (m, 2H), 6.82 (d, 2H, J=8.7 Hz), 7.07 (d, 2H, J=8.4 Hz), 7.15-7.31 (m, 5H); MS (APCI+) m/z (rel): 256 (100); [α]D=−30.4° (c=1.25 MeOH).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A sample of 3.02 g (11.8 mmol) of 1-(4′-methoxyphenyl)-2-benzylaminopropane (42) was reacted with 1.8 g (11.8 mmol) (S)-(+)-mandelic acid to give 530 mg (35% based on enantiomeric abundance) of the free amine after workup. 1H NMR (CDCl3) δ□ 1.10 (d, 3H, J=6.3 Hz), 2.57-2.76 (m, 2H), 2.88-2.94 (m, 1H), 3.79 (s, 3H), 3.72-3.88 (m, 2H), 6.82 (d, 2H, J=8.7 Hz), 7.07 (d, 2H, J=8.4 Hz), 7.15-7.31 (m, 5H); MS (APCI+) m/z (rel): 256 (100); [α]D=−30.4° (c=1.25 MeOH).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium borohydride (3.14 g) was added to an ice-cold suspension of methyl 5-(bromoacetyl)thiophene-2-carboxylate (4.14 g) in methanol (250 ml). After 15 min the reaction mixture was poured into iced water (1000 ml) and extracted with ethyl acetate (5×200 ml). The dried (MgSO4) organic phase was evaporated to give a yellow oil, which was heted with [2-(4-methoxyphenyl)-1-methylethyl](phenylmethyl)amine (5.18 g) at 100° for 16 h. The cooled reaction mixture was partitioned between water (400 ml) and ethyl acetate (3×400 ml), and the dried (MgSO4) organic phase was evaporated, giving the crude product as an oily brown solid (9.75 g). This was applied on silica to a short-path silica column (1000 g) eluted with cyclohexane 15% diethyl ether. The appropriate fractions (Rf 0.15) were combined and evaporated to give the ethanolamine (slightly impure) as an oily beige solid (2.4 g). TLC SiO2 (Et2O/cyclohexane, 1:1 ) Rf 0.39. extracted with ethyl acetate (5×200 ml) The dried (MgSO4) organic phase was evaporated to give a yellow oil, which The cooled reaction mixture was partitioned between water (400 ml) and ethyl acetate (3×400 ml) the dried (MgSO4) organic phase was evaporated giving the crude product as an oily brown solid (9.75 g) eluted with cyclohexane 15% diethyl ether evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: from 2-bromo-4′-benzyloxy-3′-nitroacetophenone and 4-methoxy-α-methyl-N-(phenylmethyl)benzeneethanamine comprising the sequential steps of: (a) reducing 2-bromo-4′-benzyloxy-3′-nitroacetophenone with about one equivalent of a borane reagent in the presence of a catalytic amount of a single enantiomer of an oxazaborolidine derived from cis 1-amino-2-indanol to produce substantially enantiomerically pure α-(bromomethyl)-4-phenylmethoxy-3-nitrobenzenemethanol (FBH); (b) reducing the α-(bromomethyl)-4-phenylmethoxy-3-nitrobenzenemethanol with hydrogen in the presence of a noble metal catalyst to produce an aniline FBH2; (c) formylating the aniline with formic acid and acetic anhydride to produce a compound of formula FBH3:

Conditions: temp:0.00; pressure:0.00; stir: