Hydrochloric Acid → HCID 11386534, compound

HRID 900337Notes

Reaction equation

HRID 900337 reaction equation
[OH-].[Na+].C[C@:4]([NH:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])([CH2:8][S:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:22]=[CH:21][C:20]([N:23]3[C:31]4[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=4)[CH:25]=[CH:24]3)=[CH:19][CH:18]=2)=[CH:13][CH:12]=1)[C:5]([O-:7])=[O:6].Cl>O1CCCC1.CO.O>[C:36]([O:35][C:33]([NH:32][C@@H:4]([CH2:8][S:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:18]=[CH:19][C:20]([N:23]3[C:31]4[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=4)[CH:25]=[CH:24]3)=[CH:21][CH:22]=2)=[CH:13][CH:12]=1)[C:5]([OH:7])=[O:6])=[O:34])([CH3:39])([CH3:37])[CH3:38]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 131726821HCID 131726821, compound

Product 1

HCID 11386534HCID 11386534, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

1N Sodium hydroxide solution (2.14 mL, 2.14 mmol) was added dropwise to a stirred solution of (2R)-Methyl-tert-butoxycarbonylamino-3-(4′-indol-1-ylbiphen-4-ylmethylsulfanyl)-propionate (552 mg, 1.07 mmol) in tetrahydrofuran (15 mL) and methanol (3 mL). The clear reaction mixture was stirred at room temperature until the reaction was complete (TLC control), and then diluted with water (10 mL), and acidified to pH 3 with 2N hydrochloric acid. The reaction mixture was extracted with ethyl acetate (2×20 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 5-10% methanol in methylene chloride as eluent, afforded the title compound has a white solid (486 mg, 90%), m.pt. 171-173° C. Rf: 0.35 (10% methanol in dichloromethane); 1H NMR (DMSO-d6, 300 MHz): δ 7.86 (2H, d, J=8 Hz, Ar—H), 7.68 (6H, m, Ar—H), 7.61 (1H, d, J=8 Hz, Ar—H), 7.43 (2H, d, J=8 Hz, Ar—H), 7.11-7.22 (2H, m, Ar—H), 6.80 (1H, br s, NH), 6.72 (1H, d, J=3.5 Hz, Ar—H), 4.06 (1H, m, CHN), 3.80 (2H, s, PhCH2), 2.86 (1H, dd, J=13, 5 Hz, CHHCHN), 2.72 (1H, dd, J=13, 8 Hz, CHHCHN), 1.40 (9H, s, CMe3), ESI-LCMS e/z calcd for C29H30N2O4S: 502.632, found 503 (M+H)+, 525 (M+Na)+.

Workup

  1. extractionThe reaction mixture was extracted with ethyl acetate (2×20 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-c674b9e8ed664a21adb986337befbd05
Source dataset
uspto-grants-2008_04
Patent number
US07358248B2

Reaction notes

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