Hydrochloric Acid → (2R)-3-[4'-(2-benzylbenzofuran-3-yl)biphen-4-ylmethylsulfanyl]-2-tert-butoxy-carbonylamino-propionic acid

HRID 900352Notes

Reaction equation

HRID 900352 reaction equation
[OH-:1].[Na+].C[O:4][C:5](=[O:46])[C@@H:6]([NH:38][C:39](OC(C)(C)C)=[O:40])[CH2:7][S:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:21]=[CH:20][C:19]([C:22]3[C:26]4[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=4[O:24][C:23]=3[CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)=[CH:18][CH:17]=2)=[CH:12][CH:11]=1.Cl>O1CCCC1.CO>[CH2:31]([C:23]1[O:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[C:22]=1[C:19]1[CH:20]=[CH:21][C:16]([C:13]2[CH:14]=[CH:15][C:10]([CH2:9][S:8][CH2:7][C@:6]([N:38]=[C:39]=[O:40])([O:1][C:10]([CH3:15])([CH3:11])[CH3:9])[C:5]([OH:4])=[O:46])=[CH:11][CH:12]=2)=[CH:17][CH:18]=1)[C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 131726824(2R)-Methyl-3-[4'-(2-benzylbenzofuran-3-yl)biphen-4-ylmethylsulfanyl]-2-tert-butoxycarbonylaminopropionate

Product 1

HCID 131726825(2R)-3-[4'-(2-benzylbenzofuran-3-yl)biphen-4-ylmethylsulfanyl]-2-tert-butoxy-carbonylamino-propionic acidYield 84%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

1N Sodium hydroxide (2 mL) was added to a stirred solution of (2R)-methyl-3-[4′-(2-benzylbenzofuran-3-yl)biphen-4-ylmethylsulfanyl]-2-tert-butoxycarbonylamino-propionate (100 mg) in a mixture of tetrahydrofuran (6 mL) and methanol (2 mL). The solution was stirred for 1 hour and then acidified to pH 3 with 1N hydrochloric acid. The reaction mixture was extracted with ethyl acetate (3×10 mL). The combined extract was washed with water, brine, dried over anhydrous MgSO4, filtered and concentrated in vacuo. Purification of the product by flash column chromatography, using 5% methanol in methylene chloride as eluent, afforded the title compound as a white solid (82 mg, 84%): mp. 89-90° C. Rf=0.50 (10% methanol in dichloromethane). 1H NMR (DMSO-d6, 300 MHz) δ 7.8 (2H, d, J=9 Hz, Ar—H), 7.6 (6H, m, Ar—H), 7.4 (2H, d, J=9 Hz, Ar—H), 7.28 (5H, m, Ar—H), 7.21 (2H, d, J=8 Hz, Ar—H), 6.42 (1H, d, J=8 Hz, NH), 4.26 (2H, s, PhCH2), 3.95 (1H, m, CHN), 3.75 (2H, s, PhCH2S), 2.9 (1H, dd, J=15, 5 Hz, CHHCHN), 2.74 (1H, dd, J=15, 8 Hz, CHHCHN), 1.39 (9H, s, tBu); ESI-LCMS e/z calcd for C36H35NO5S 593.74, found 617 (M+Na)+.

Workup

  1. extractionThe reaction mixture was extracted with ethyl acetate (3×10 mL)
  2. extractionThe combined extract
  3. washwas washed with water, brine
  4. dry with materialdried over anhydrous MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification of the product by flash column chromatography

Sources & evidence

ORD record
ord-d7cf20e4368e40aa930e7e101086eece
Source dataset
uspto-grants-2008_04
Patent number
US07358248B2

Reaction notes

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