Reaction #1563919

Reaction equation

carbon monoxide

(S)—N-tert-butoxycarbonyl-1-(4-bromophenyl)ethylamine

CH3CN

triethylamine

→

title compound

Yield 143.2%

methyl (S)-4-(1-tert-butoxycarbonylaminoethyl)benzoate

Yield 143.2%

Solvents

CH3OH

Conditions

Workup

1. 1
   OtherSeal the vessel
2. 2
   Othertransfer to a round-bottomed flask
3. 3
   Washrinsing with CH3OH
4. 4
   ConcentrationConcentrate the mixture under reduced pressure
5. 5
   Otherto furnish an orange residue
6. 6
   ExtractionAdd water (50 mL), then extract with EtOAc (2×50 mL)
7. 7
   WashWash the combined organic phases with saturated aqueous NaCl (25 mL)
8. 8
   Otherseparate the layers
9. 9
   Dryingdry the organic phase over MgSO4
10. 10
    Filtrationfilter
11. 11
    Otherto remove the solids
12. 12
    Concentrationconcentrate the filtrate under reduced pressure
13. 13
    Otherto give crude product
14. 14
    OtherPurify the product by flash chromatography on silica gel eluting with a gradient of 0% to 60% EtOAc/hexanes
15. 15
    ConcentrationConcentrate the fractions
16. 16
    workup.ADDITIONcontaining the desired product under reduced pressure

Procedure

To a Parr autoclave with mechanical stirring, add Pd(OAc)2 (120 mg, 0.53 mmol), 1,1′-bis(diphenylphosphino)ferrocene (355 mg, 0.64 mmol), (S)—N-tert-butoxycarbonyl-1-(4-bromophenyl)ethylamine (1.50 g, 5.0 mmol), anhydrous CH3CN (45 mL), anhydrous CH3OH (30 mL), and triethylamine (1.9 mL, 13.63 mmol). Seal the vessel and pressurize with carbon monoxide to 724 kPag. Heat the vessel to 85° C. and stir the mixture overnight. Vent the reaction vessel (Caution—poison gas!) and transfer to a round-bottomed flask, rinsing with CH3OH. Concentrate the mixture under reduced pressure to furnish an orange residue. Add water (50 mL), then extract with EtOAc (2×50 mL). Wash the combined organic phases with saturated aqueous NaCl (25 mL), then separate the layers, dry the organic phase over MgSO4, filter to remove the solids, and concentrate the filtrate under reduced pressure to give crude product. Purify the product by flash chromatography on silica gel eluting with a gradient of 0% to 60% EtOAc/hexanes. Concentrate the fractions containing the desired product under reduced pressure to furnish the title compound as a white solid (1.00 g, 72% yield). Mass spectrum (m/z) 224 (M+2H−t-Bu)+, 302 (M+Na)+, 581 (2M+Na)+. 1H NMR (400 MHz, DMSO-d6): δ 7.89 (d, =8.4 Hz, 2H), 7.41 (d, J=8.2 Hz, 2H), 4.64 (dq, J=7.4, 6.8 Hz, 1H), 3.82 (s, 3H), 1.34 (br s, 9H), 1.28 (d, J=7.2 Hz, 3H).

Source