Hydrochloric Acid → HCID 15605608, compound

HRID 1994173Notes

Reaction equation

CC1(C)C(C)(C)OB([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[S:16][CH:17]=[CH:18][C:19]=3[NH:20][S:21]([CH:24]([CH3:26])[CH3:25])(=[O:23])=[O:22])=[CH:11][CH:10]=2)O1.C([O:30][C:31](=[O:42])[C:32]1[CH:37]=[CH:36][C:35](I)=[C:34]([O:39][CH2:40][CH3:41])[CH:33]=1)C.COCCOC.C(O)C.C([O-])([O-])=O.[Na+].[Na+].O.[OH-].[Na+].Cl.CCCCCCC.CCCCCCC.CC(C)=O>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:40]([O:39][C:34]1[CH:33]=[C:32]([C:31]([OH:42])=[O:30])[CH:37]=[CH:36][C:35]=1[C:9]1[CH:10]=[CH:11][C:12]([C:15]2[S:16][CH:17]=[CH:18][C:19]=2[NH:20][S:21]([CH:24]([CH3:25])[CH3:26])(=[O:22])=[O:23])=[CH:13][CH:14]=1)[CH3:41]

Participants

Conditions

Temperature: 60 °C

Procedure

Mix propane-2-sulfonic acid {2-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl) -phenyl]-thiophen-3-yl}-amide (1.00 equiv; 441.02 mmoles; 196.60 g), 3-ethoxy-4-iodo -benzoic acid ethyl ester (1.00 equiv; 441.47 mmoles; 141.27 g), DME (15.15 moles; 1.57 L; 1.37 kg), PdCl2(dppf) (2.42 mmoles; 1.97 g), and ethanol (13.57 moles; 790.00 mL; 625.13 g) under a N2 atmosphere. Then add Na2CO3 2M in water (1.89 equiv; 833.06 mmoles; 416.53 mL; 504.00 g) and heat the reaction mixture to reflux until HPLC monitoring indicates reaction completion. Cool reaction mixture to RT then add water (109.13 moles; 1.97 L). Separate the organic layer, filter through diatomaceous earth, then concentrate organic layer under reduced pressure. Add ethanol (2.36 L), and remove solvent under reduced pressure. Add 3-Mercaptopropyl-functionalized Silica Gel (50.00 g), and heat to 60° C. for 30 minutes. Cool to RT then filter over diatomaceous earth. Rinse cake with ethanol, then combine ethanol washes and filtrate. Add 14% Sodium Hydroxide (4.89 moles; 1.27 L; 1.43 kg) and heat the reaction mixture at 55° C. until monitoring by HPLC indicates the end of the reaction. Cool to RT then add 7N HCl to the reaction mixture. Stir the resulting precipitate overnight. Filter the reaction mixture and wash cake with EtOH/Water (40/60-v/v) (180.78 g), EtOH (155.49 g), and n-heptane (262 g). Redissolve cake in acetone (2.18 kg) and add activated charcoal (46 g). Heat the reaction mixture at 50° C. for 30 minutes. Cool to RT, filter over diatomaceous earth (765.59 mmoles; 200.00 g), and concentrate under reduced pressure. Cool to RT, then add n-Heptane (7.73 moles; 1.13 L; 775. 00 g) and stir for 1 h. Fltere and wash cake with n-heptane/acetone 60/40 (2.58 moles; 354.79 mL) and dry under reduced pressure to yield 124 g of the title compound.

Workup

temperatureto reflux until HPLC monitoring
customreaction completion
temperatureCool
customreaction mixture to RT
customSeparate the organic layer
filtrationfilter through diatomaceous earth
customAdd ethanol (2.36 L), and remove solvent under reduced pressure
temperatureCool to RT
filtrationthen filter over diatomaceous earth
washRinse cake with ethanol
temperatureheat the reaction mixture at 55° C. until monitoring by HPLC
customthe end of the reaction
temperatureCool to RT
filtrationFilter the reaction mixture
washwash cake with EtOH/Water (40/60-v/v) (180.78 g), EtOH (155.49 g), and n-heptane (262 g)
dissolutionRedissolve cake in acetone (2.18 kg)
additionadd activated charcoal (46 g)
temperatureHeat the reaction mixture at 50° C. for 30 minutes
temperatureCool to RT
filtrationfilter over diatomaceous earth (765.59 mmoles; 200.00 g)
concentrationconcentrate under reduced pressure
temperatureCool to RT
customdry under reduced pressure

Sources & evidence

ORD record: ord-9e6bb47e97ed42278b0dcc1fa3022cc0
Source dataset: uspto-grants-2010_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07652064B2

Reaction notes

Loading…