Hydrochloric Acid → N-[4-Hydroxymethyl-2-(2-methylphenyl)benzoyl]methionine methyl ester

HRID 2121270Notes

Reaction equation

HRID 2121270 reaction equation
[OH:1][CH2:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=O)=[C:5]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[CH3:18])[CH:4]=1.[CH3:19][O:20][C:21](=[O:28])[C@H:22]([CH2:24][CH2:25][S:26][CH3:27])[NH2:23].Cl.ON1C2C=CC=CC=2N=N1.C(N=C=NCCCN(C)C)C.C(N(CC)CC)C>CN(C=O)C.CCOC(C)=O>[CH3:19][O:20][C:21](=[O:28])[C@H:22]([CH2:24][CH2:25][S:26][CH3:27])[NH:23][C:7](=[O:9])[C:6]1[CH:10]=[CH:11][C:3]([CH2:2][OH:1])=[CH:4][C:5]=1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[CH3:18]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 64684methyl (2S)-2-amino-4-(methylsulfanyl)butanoateHCID 757711-HydroxybenzotriazoleHCID 106339044-Hydroxymethyl-2-(2-methylphenyl)benzoic acid

Product 1

HCID 54396972N-[4-Hydroxymethyl-2-(2-methylphenyl)benzoyl]methionine methyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-Hydroxymethyl-2-(2-methylphenyl)benzoic acid (69 g, 285 mmol), prepared as in example 1075E, L-methionine methyl ester.HCl (68.3 g, 342 mmol), 1-hydroxybenzotriazole (46.2 g, 342 mmol), and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (65.6 g, 342 mmol) were dissolved at ambient temperature in DMF (700 mL). To this solution was added triethylamine (47.7 mL, 342 mmol) and the resulting thick slurry was stirred overnight at ambient temperature. The reaction was diluted with EtOAc (700 mL) and washed with water (2×1L), saturated NaHCO3 (2×500 mL), 1N H3PO4 (2×500 mL), and brine. Organic layer dried with Na2SO4, filtered, and concentrated in vacuo to produce a pale yellow solid (110 g, 100% crude yield). 1H(300 MHz, CDCl3) δ 7.93 (1H, m), 7.44 (1H, dd, J=8, 2 Hz), 7.40-7.20 (4H, m), 7.19 (1H, bs), 5.92 (1H, m), 4.78 (2H, s), 4.63 (1H, m), 3.66 (3H, s), 2.20-2.00 (8H, m), 1.87 (1H, m), 1.75 (1H, m), 1.60 (1H, m). m/e (ESI) 386 (MH−).

Workup

  1. washwashed with water (2×1L), saturated NaHCO3 (2×500 mL), 1N H3PO4 (2×500 mL), and brine
  2. dry with materialOrganic layer dried with Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto produce a pale yellow solid (110 g, 100% crude yield)

Sources & evidence

ORD record
ord-a109ff892af2449f93e60335b6630934
Source dataset
uspto-grants-2004_02
Patent number
US06693123B2

Reaction notes

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