tert-Butyl piperazine-1-carboxylate → 1-(4-Chloro-3-isopropoxy-phenyl)-piperazine

Temperature

85 °C

1-Bromo-3-isopropoxy-4-chlorobenzene (preparation described elsewhere) was combined with 1.11 g (6 mmol) of 1-Bocpiperazine, 672 mg (7.0 mmol) of sodium tert-butoxide, 93 mg (0.15 mmol) of rac-2,2′-Bis(diphenylphosphine)-1,1′-binaphthyl, and 45 mg (0.05 mmol) Tris(dibenzylideneacetone)dipalladium (0) in a flask under an N2 atmosphere, and the mixture was heated at 85° C. for 3.5 hours. The resulting residue was partitioned between a 1/1 mixture of ether and ethyl acetate and water, and the phases were separated. The ether/ethyl acetate phase was diluted with one volume of hexanes, washed twice with 0.5M pH=7 phosphate buffer, and once each with 1M NaOH and brine. The final organic phase was dried over Na2SO4, filtered, and concentrated in vacuo to an oil. The oil was dissolved in ethyl acetate, 10 mL each of 2M HCl in ether and methanol were added, and the product was isolated by filtration after crystallization. 1H NMR (D2O, 400 MHz): 7.23 (d, 1H), 6.69 (s, 1H), 6.59 (d, 1H), 4.53 (m, 1H), 3.28 (m, 8H), 1.20 (d, 6H) ppm.

1. customThe resulting residue was partitioned between a 1/1 mixture of ether and ethyl acetate and water
2. customthe phases were separated
3. additionThe ether/ethyl acetate phase was diluted with one volume of hexanes
4. washwashed twice with 0.5M pH=7 phosphate buffer
5. dry with materialThe final organic phase was dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo to an oil
8. dissolutionThe oil was dissolved in ethyl acetate
9. addition10 mL each of 2M HCl in ether and methanol were added
10. customthe product was isolated by filtration
11. customafter crystallization

ORD record

ord-7f59b23909004ef98bbd2fd00098abf2

Source dataset

uspto-grants-2007_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07157464B2