Isopropyl chloroformate → 3-[4-Hydroxy-2-(isopropoxycarbonylamino-methyl)-phenyl]-propionic acid tert-butyl ester

HRID 1181041Notes

Reaction equation

HRID 1181041 reaction equation
[C:1]([O:5][C:6](=[O:18])[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][C:10]=1[CH2:16][NH2:17])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.Cl[C:27]([O:29][CH:30]([CH3:32])[CH3:31])=[O:28]>C(Cl)Cl.ClC(OC(C)C)=O>[C:1]([O:5][C:6](=[O:18])[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][C:10]=1[CH2:16][NH:17][C:27]([O:29][CH:30]([CH3:32])[CH3:31])=[O:28])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 7917Isopropyl chloroformateHCID 8471TriethylamineHCID 17984622Tert-butyl-3-[2-(aminomethyl)-4-hydroxyphenyl]propanoate

Product 1

HCID 589794703-[4-Hydroxy-2-(isopropoxycarbonylamino-methyl)-phenyl]-propionic acid tert-butyl esterYield 94.3%

Reagents, catalysts & solvents 2

HCID 7917Isopropyl chloroformateCatalystHCID 6344DichloromethaneSolvent

Procedure

A slurry of 3-(2-aminomethyl-4-hydroxy-phenyl)-propionic acid tert-butyl ester (75.4 g, 0.3 mol) in CH2Cl2 (900 mL) at 1° C. was treated with triethylamine (60.7 g, 0.6 mol). Isopropyl chloroformate (300 mL, 0.3 mol, 1M in toluene) was added while maintaining the temperature less than 12° C. The resulting solution was stirred 16 h at ambient temperature. After 16 h, additional isopropyl chloroformate (15 mL, 0.015 mol, 1.0M in toluene) was added, and the reaction was stirred for 1 h. The reaction mixture was washed with 1N HCl (2×200 mL) and saturated NaHCO3 solution (2×200 mL). The organic layer was dried (Na2SO4) and concentrated. The residue was purified by filtration through Merck silica gel 62 (750 grams, CH2Cl2/MeOH 100/0 to 96/4) to give the title compound (95.48 g, 94.3%). 1H NMR (300 MHz, CDCl3): δ 1.20-1.24 (d, 6H), 1.40 (s, 9H), 2.46-2.52 (t, 2H), 2.81-2.86 (t, 2H), 4.294.32 (d, 2H), 4.86-4.97 (m, 1H), 5.19-5.28 (m, 1H), 6.67-6.72 (dd, 2H), 6.76 (s, 1H), 6.97-7.00 (d, 1H). MS (ES−) m/z 336.1 [M−H]−.

Workup

  1. temperaturewhile maintaining the temperature less than 12° C
  2. waitAfter 16 h
  3. stirringthe reaction was stirred for 1 h
  4. washThe reaction mixture was washed with 1N HCl (2×200 mL) and saturated NaHCO3 solution (2×200 mL)
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. concentrationconcentrated
  7. filtrationThe residue was purified by filtration through Merck silica gel 62 (750 grams, CH2Cl2/MeOH 100/0 to 96/4)

Sources & evidence

ORD record
ord-13a3bcd2a20b48f29f0e1dfc32c6c7a3
Source dataset
uspto-grants-2007_10
Patent number
US07282501B2

Reaction notes

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