Hydrochloric Acid → (R)-benzyl 3-amino-4-(3'-chlorobiphenyl-4-yl)butanoate hydrochloride

HRID 1945019Notes

Reaction equation

HRID 1945019 reaction equation
[NH2:1][C@H:2]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[CH:22]=2)=[CH:17][CH:16]=1)[CH2:3][C:4]([O:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:5].Cl.O1CCOCC1>>[ClH:27].[NH2:1][C@H:2]([CH2:14][C:15]1[CH:16]=[CH:17][C:18]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[CH:22]=2)=[CH:19][CH:20]=1)[CH2:3][C:4]([O:6][CH2:7][C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)=[O:5]

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 59607598(R)-benzyl 3-amino-4-(3'-chlorobiphenyl-4-yl)butanoate

Product 1

HCID 86648193(R)-benzyl 3-amino-4-(3'-chlorobiphenyl-4-yl)butanoate hydrochloride

Procedure

To (R)-benzyl 3-amino-4-(3′-chlorobiphenyl-4-yl)butanoate (87.6 mg, 0.183 mmol) is added a solution of HCl in 1,4-dioxane (0.456 mL, 1.825 mmol) at room temperature. After stirring for 3 hours, the reaction mixture is concentrated under reduced pressure to give (R)-benzyl 3-amino-4-(3′-chlorobiphenyl-4-yl)butanoate hydrochloride. A mixture of (R)-benzyl 3-amino-4-(3′-chlorobiphenyl-4-yl)butanoate hydrochloride, fumaric acid monoethyl ester (33.4 mg, 0.220 mmol), EDCl (63.3 mg, 0.330 mmol), DIPEA (0.058 ml, 0.330 mmol) and HOAt (44.9 mg, 0.330 mmol) in DMF (1.8 ml) is allowed to stir at room temperature for 3 hour. The reaction mixture is diluted with water, and then the products are extracted with EtOAc. The organic layer is washed with NH4OH, 1M HClaq and brine, dried over Na2SO4, filtered, and concentrated to give crude. The obtained residue is purified by silica gel flash column chromatography (heptane/EtOAc=100:0 to 0:100) to give (R,E)-ethyl 4-(4-(benzyloxy)-1-(3′-chlorobiphenyl-4-yl)-4-oxobutan-2-ylamino)-4-oxobut-2-enoate (72.9 mg); HPLC retention time=1.40 minutes (condition B); MS (m+1)=506.3; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.31 (t, J=7.1 Hz, 3H) 2.58 (A of ABX, Jab=16.4 Hz, Jax=5.3 Hz, 1H) 2.6 (B of ABX, Jab=16.4 Hz, Jbx=5.1 Hz, 1H) 2.88 (A of ABX, Jab=13.6 Hz, Jax=8.1 Hz, 1H) 3.03 (B of ABX, Jab=13.6 Hz, Jbx=6.3 Hz, 1H) 4.24 (q, J=7.1 Hz, 2H) 4.56-4.64 (m, 1H) 5.12 (A of AB, J=12.1 Hz, 1H) 5.18 (B of AB, J=12.1 Hz, 1H) 6.57 (br d, J=9.1 Hz, 1H) 6.77 (A of AB, J=15.4 Hz, 1H) 6.81 (B of AB, J=15.4 Hz, 1H) 7.19 (br d, J=8.1 Hz, 2H) 7.29-7.47 (m, 10H) 7.53-7.54 (m, 1H).

Workup

  1. concentrationthe reaction mixture is concentrated under reduced pressure

Sources & evidence

ORD record
ord-6da36717b1ae4801811e1ce81b81869e
Source dataset
uspto-grants-2013_03
Patent number
US08394853B2

Reaction notes

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