Diisopropylethylamine → [4-(1-Hydroxy-3-cyclohexylprop-2-ylaminomethyl)-2-(2-methylphenyl)benzoyl]methionine

HRID 325240Notes

Reaction equation

HRID 325240 reaction equation
C([O:3][C:4](=[O:28])[C@H:5]([CH2:24][CH2:25][S:26][CH3:27])[NH:6][C:7](=[O:23])[C:8]1[CH:13]=[CH:12][C:11]([CH:14]=[O:15])=[CH:10][C:9]=1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[CH3:22])C.OCC1C=CC(C(O)=O)=C(C2C=CC=CC=2)C=1.Cl.[NH2:47][C@@H:48]([CH2:51][CH:52]1[CH2:57][CH2:56][CH2:55][CH2:54][CH2:53]1)[CH2:49]O.C(N(C(C)C)CC)(C)C.C([BH3-])#N.[Na+].BrC1(C)C(O)=CC=CC1.Cl.C(O)C>C1(C)C=CC=CC=1.C(O)C>[OH:15][CH:14]([NH:47][CH:48]([CH2:51][CH:52]1[CH2:57][CH2:56][CH2:55][CH2:54][CH2:53]1)[CH3:49])[C:11]1[CH:12]=[CH:13][C:8]([C:7]([NH:6][C@H:5]([C:4]([OH:3])=[O:28])[CH2:24][CH2:25][S:26][CH3:27])=[O:23])=[C:9]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[CH3:22])[CH:10]=1

Participants

10

Reactant 7

HCID 81531DiisopropylethylamineHCID 5003444Sodium cyanoborohydrideHCID 16212813(2S)-2-amino-3-cyclohexylpropan-1-ol hydrochlorideHCID 21887872Ethanol hydrochlorideHCID 234364204-Hydroxymethyl-2-phenylbenzoic acidHCID 696519946-Bromo-6-methylcyclohexa-1,3-dien-1-olHCID 86756645[4-Formyl-2-(2-methylphenyl)benzoyl]methionine ethyl ester

Product 1

HCID 70226063[4-(1-Hydroxy-3-cyclohexylprop-2-ylaminomethyl)-2-(2-methylphenyl)benzoyl]methionineYield 106.4%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 1140TolueneSolvent

Procedure

A mixture of [4-formyl-2-(2-methylphenyl)benzoyl]methionine ethyl ester (614 mg, 1.54 mmol), prepared according to Example 158F except substituting [4-hydroxmethyl-2-(2-methylphenyl)benzoic acid for 4-hydroxymethyl-2-phenylbenzoic acid in Example 158E, (S)-(+)-2-amino-3-cyclohexyl-1-propanol hydrochloride (357 mg, 1.84 mmol) and diisopropylethylamine (0.135 mL, 0.77 mmol) in toluene was refluxed for 5 hours using a Dean-Stark apparatus. The reaction mixture was cooled to ambient temperature and diluted with ethanol. Sodium cyanoborohydride (145 mg) and o-bromocresol green was added. The reaction mixture was stirred while acidity was maintained using HCl-ethanol. The reaction was quenched with saturated aqueous potassium carbonate and the mixture was extracted with dichloromethane (2×). The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo. Chromatography on silica gel (5% methanol-chloroform) gave the desired compound (840 mg).

Workup

  1. customprepared
  2. temperaturewas refluxed for 5 hours
  3. temperaturewas maintained
  4. customThe reaction was quenched with saturated aqueous potassium carbonate
  5. extractionthe mixture was extracted with dichloromethane (2×)
  6. dry with materialThe combined organic layers were dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-2a48589469404b5186536ea28ea9d642
Source dataset
uspto-grants-2001_04
Patent number
US06221865B1

Reaction notes

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