tert-butyl N-methyl-N-(2-oxoethyl)carbamate

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

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

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

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

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

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

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

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

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: To an oven dried, argon purged flask fitted with a magnetic stirbar was added tert-butyl methyl(2-oxoethyl)carbamate (0.135 g, 0.777 mmol), and DCE (10 mL). At this time, stirring began, and 6-nitro-3,4-dihydro-2H-benzo[b][1,4]oxazine (0.10 g, 0.555 mmol) was added, followed by acetic acid (0.064 mL, 1.110 mmol) and sodium triacetoxyborohydride (0.294 g, 1.388 mmol). The resulting mixture stirred overnight at room temperature. After 18 hours, the reaction was quenched by the addition of saturated NaHCO3 (10 mL) and extracted with CH2Cl2. The aqueous layer was extracted further, and the combined organics were washed with brine, dried (Na2SO4), and concentrated. The crude product was combined with the product of a second reaction (prepared in accordance with the above procedure, with the omission of acetic acid). The combined products were purified on silica gel eluting with 50-70% EtOAc/hexanes to yield the title compound as a yellow residue (130 mg, 34.7%). 1H NMR (DMSO-d6) δ 7.58-7.37 (m, 2H), 6.92-6.80 (m, 1H), 4.25 (t, 2H, J=4.2 Hz), 3.58-3.36 (m, 6H), 2.87-2.74 (m, 3H), 1.27, 1.18 (2×s, 9H); ESI-MS (m/z, %): 360 (MNa+, 100). To an oven dried argon purged flask fitted with a magnetic stirbar The resulting mixture stirred overnight at room temperature the reaction was quenched by the addition of saturated NaHCO3 (10 mL) extracted with CH2Cl2 The aqueous layer was extracted further the combined organics were washed with brine dried (Na2SO4) concentrated The crude product was combined with the product of a second reaction ( The combined products were purified on silica gel eluting with 50-70% EtOAc/hexanes

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

Procedure: To a solution of ethyl 3-fluoro-4-piperidinylacetate (230 mg, 1.22 mmol) and 2-(N-tert-butoxy carbonyl-N-methylamino)acetaldehyde (211 mg, 1.22 mmol) in THF (5 mL) was added NaBH(OAc)3 (386 mg, 1.82 mmol) and acetic acid (70.0 mL, 1.22 mmol) at room temperature After being sired for 24 hr, the reaction mixture was quenched by the addition of sat. NaHCO3 solution and extracted with EtOAc. The extracts were washed with brine, dried over Na2CO3, and concentrated to dryness. Chromatography of the residue with CHCl3—MeOH (6:1, v/v) as eluent gave ethyl 3-fluoro-1-[2-(N-tert-butoxycarbonyl-N-methylamino)ethyl]-4-piperidinylacetate (236 mg, 56%) as a reddish oil. 1H-NMR (CDCl3) δ1.25 (t, J=7.1 Hz, 3H), 1.45 (s, 9H), 1.53 1.79 (m, 2H), 1.90-2.09 (m, 2H), 2.15 (dd, J=16.4, 7.1 Hz, 1H), 2.45-2.58 (m, 2H), 2.87 (s, 3H), 2.90-2.99 (m, 2H), 3.20 (m, 1H), 3.24-3.45 (m, 2H), 4.14 (q, J=7.1 Hz, 2H), 4.61, 4.73 (each broad s, 1H); ESI-MS m/z 347. the reaction mixture was quenched by the addition of sat. NaHCO3 solution extracted with EtOAc The extracts were washed with brine dried over Na2CO3 concentrated to dryness