Hydrochloric Acid → (R)-N-(4,5-difluoro-6-((2-fluoro-4-iodophenyl)amino)benzofuran-7-yl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide

HRID 1261404Notes

Reaction equation

HRID 1261404 reaction equation
C([O:8][C@@H:9]([CH2:38][O:39]CC1C=CC=CC=1)[CH2:10][C:11]1([S:14]([NH:17][C:18]2[C:26]3[O:25][CH:24]=[CH:23][C:22]=3[C:21]([F:27])=[C:20]([F:28])[C:19]=2[NH:29][C:30]2[CH:35]=[CH:34][C:33]([I:36])=[CH:32][C:31]=2[F:37])(=[O:16])=[O:15])[CH2:13][CH2:12]1)C1C=CC=CC=1.B(Cl)(Cl)Cl.Cl.CCCCCCC>C(Cl)Cl.C(OCC(C)C)(=O)C>[F:27][C:21]1[C:22]2[CH:23]=[CH:24][O:25][C:26]=2[C:18]([NH:17][S:14]([C:11]2([CH2:10][C@@H:9]([OH:8])[CH2:38][OH:39])[CH2:12][CH2:13]2)(=[O:15])=[O:16])=[C:19]([NH:29][C:30]2[CH:35]=[CH:34][C:33]([I:36])=[CH:32][C:31]=2[F:37])[C:20]=1[F:28]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8900HeptaneHCID 25135Boron TrichlorideHCID 71087258(R)-1-(2,3-bis(benzyloxy)propyl)-N-(4,5-difluoro-6-((2-fluoro-4-iodophenyl)amino)benzofuran-7-yl)cyclopropane-1-sulfonamide

Product 1

HCID 71087417(R)-N-(4,5-difluoro-6-((2-fluoro-4-iodophenyl)amino)benzofuran-7-yl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamideYield 65.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8038Isobutyl AcetateSolvent

Procedure

To a solution of (R)-1-(2,3-bis(benzyloxy)propyl)-N-(4,5-difluoro-6-((2-fluoro-4-iodophenyl)amino)benzofuran-7-yl)cyclopropane-1-sulfonamide (140 g, 183.6 mmol) in DCM (700 mL) was added 1M BCl3 solution in DCM (1.8 L, 1.84 mol) at −65-70° C. The mixture was stirred at −65˜−70° C. for 30 minutes until HPLC analysis showed the reaction had gone to completion. The cold solution was added to 1N HCl solution (1.8 L) at below 15° C., stirred for 15 mins and separated. The DCM layer was washed with water (2 L), the brine (1.5 L). DCM layer was concentrated to ˜250 mL and filtered to give white solid. The solid was dissolved in isobutyl acetate (240 mL) and heptane (500 mL) was added. The suspension was stirred overnight, filtered and dried to give 70 g of (R)—N-(4,5-difluoro-6-((2-fluoro-4-iodophenyl)amino)benzofuran-7-yl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide with 98.4% purity (65.5% yield, ee>99%).

Workup

  1. stirringstirred for 15 mins
  2. customseparated
  3. washThe DCM layer was washed with water (2 L)
  4. concentrationDCM layer was concentrated to ˜250 mL
  5. filtrationfiltered
  6. customto give white solid
  7. stirringThe suspension was stirred overnight
  8. filtrationfiltered
  9. customdried

Sources & evidence

ORD record
ord-dffce4a26dc84c9f8d9b13a03152581b
Source dataset
uspto-grants-2013_06
Patent number
US08470878B2

Reaction notes

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