L-3,4-DIFLUOROPHENYLALANINE

Off-white solid powder

General procedure: The suitable aldehyde 1j-l, 1n or 1o (0.5 mmol), malonic acid (1.0 mmol) and piperidine (0.01 mmol) were dissolved in DMSO (500 mL) and the mixture was heated in a microwave reactor (30 min, 60 C). After cooling, ammonia solution (9.5 mL, 13percent w/v, approx. 7 M, adjusted to pH 10.0 by slow addition of dry ice chunks) was added, followed by E. coli BL21(DE3) cells overproducing the required PAL (400 mg wet cell paste). The suspension was stirred at 37 C for several hours, monitoring the conversion by HPLC. For product isolation, the reaction mixture was acidified to pH <2.0 using aqueous H2SO4 (20percent w/v) and centrifuged (8000 rpm, 5 min) to remove cells and precipitated unconverted substrate. Dowex 50WX8 hydrogen form resin (5.0 g), packed in a disposable plastic column, was washed with deionised water (20 mL) and aqueous H2SO4 (20 mL, 5percent w/v). The supernatant from the biotransformation was loaded onto the resin (1 mL min1). The resin bed was washed with deionised water until the flow-through tested neutral, then the product was eluted with aqueous NH4OH (20 mL, 5percent w/v). Fractions containing the product were pooled and dried overnight in a centrifugal evaporator, to afford the corresponding L-phenylalanine L-3j-l, L-3n or L-3o as a white solid. 4.7.1. (S)-2-Amino-3-(3, 4-difluorophenyl)propanoic acid (L-3j). Yield: 84 mg (84percent), 99percent ee by HPLC. 1H NMR (D2ONaOH, 400 MHz), d: 7.03e7.18 (m, 2H), 6.90e6.99 (m, 1H), 3.36e3.44 (m, 1H), 2.81e2.90 (dd, J13.6, 6.0 Hz, 1H), 2.70e2.79 (dd, J13.6, 7.2 Hz, 1H). 13C NMR (D2ONaOH, 101 MHz), d: 182.06, 150.94 (dd, 1JCF243 Hz, 2JCF12 Hz), 150.09 (dd, 1JCF242 Hz, 2JCF13 Hz), 135.33 (dd, 3JCF5 Hz, 4JCF3 Hz), 125.51 (dd, 3JCF6 Hz, 4JCF3 Hz), 117.83 (d, 2JCF17 Hz), 116.97 (d, 2JCF17 Hz), 57.33, 39.94. HRMS(ESI), m/z: calcd mass 202.0680 [MH], found 202.0689 [MH].

Molecular Weight:201.17
XLogP3:-1.8
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:3
Exact Mass:201.06013485
Monoisotopic Mass:201.06013485
Topological Polar Surface Area:63.3
Heavy Atom Count:14
Complexity:213
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes