Monomethyl terephthalate → HCID 69817809, compound

HRID 2417437Notes

Reaction equation

HRID 2417437 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@H:9]([N:12]([CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:13][C@H:14]([OH:23])[CH2:15][O:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:10][OH:11])=[CH:4][CH:3]=1.C/C(/O[Si](C)(C)C)=N\[Si](C)(C)C.[CH3:43][O:44][C:45]([C:47]1[CH:55]=[CH:54][C:50]([C:51](O)=[O:52])=[CH:49][CH:48]=1)=[O:46].O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>ClCCCl.C(OCC)(=O)C.O1CCCC1>[CH2:24]([N:12]([C@H:9]([CH2:10][OH:11])[CH2:8][C:5]1[CH:6]=[CH:7][C:2]([NH:1][C:51]([C:50]2[CH:54]=[CH:55][C:47]([C:45]([O:44][CH3:43])=[O:46])=[CH:48][CH:49]=2)=[O:52])=[CH:3][CH:4]=1)[CH2:13][C@H:14]([OH:23])[CH2:15][O:16][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1

Participants

10

Reactant 6

HCID 15513Monomethyl terephthalateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2724141Tetrabutylammonium FluorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 6913588N,O-bis(trimethylsilyl)acetamide2×HCID 69817666HCID 69817666, compound

Product 1

HCID 69817809HCID 69817809, compoundYield 31.5%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of (2S)-3-(4-aminophenyl)-2-[N-benzyl-N-[(2S)-2-hydroxy-3-phenoxypropyl)amino)-1-propanol (300 mg) in 1,2-dichloroethane (3.0 ml) was added N,O-bis(trimethylsilyl)acetamide (182 μl) and the solution was stirred at room temperature for 1 hour. To the solution were added successively 4-(methoxycarbonyl)benzoic acid (160 mg), 1-hydroxybenzotriazole hydrate (120 mg), and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (170 mg) at room temperature. After stirring at the same temperature for 3 hours, N,O-bis(trimethylsilyl)acetamide (182 μl) was added and the mixture was stirred overnight. The mixture was diluted with ethyl acetate (30 ml) and washed with a saturated aqueous sodium bicarbonate solution (30 ml×1), water (30 ml×2) and brine (30 ml×1) successively, dried over magnesium sulfate, and evaporated to give a yellow solid. The solid was dissolved in tetrahydrofuran (3.0 ml). To the solution was added a 1.0 M solution of tetrabutylammonium fluoride in tetrahydrofuran (1.48 ml) at room temperature and the solution was stirred for 10 minutes. The solution was diluted with ethyl acetate (20 ml) and washed with water (20 ml×2) and brine (20 ml×1) successively, dried over magnesium sulfate, and evaporated to give a yellow solid. The crude product was purified by a recycling preparative high pressure liquid chromatography equipped with a gel permeation chromatography column (eluent: chloroform) and silica gel chromatography (eluent: hexane/ethyl acetate=1/1) to give methyl 4-[[[4-[(2S)-2-[N-benzyl-N-[(2S)-2-hydroxy-3-phenoxypropyl]amino]-3-hydroxypropyl]phenyl]amino]carbonyl]benzoate (132 mg) as a pale yellow solid.

Workup

  1. stirringAfter stirring at the same temperature for 3 hours
  2. stirringthe mixture was stirred overnight
  3. washwashed with a saturated aqueous sodium bicarbonate solution (30 ml×1), water (30 ml×2) and brine (30 ml×1) successively
  4. dry with materialdried over magnesium sulfate
  5. customevaporated
  6. customto give a yellow solid
  7. stirringthe solution was stirred for 10 minutes
  8. washwashed with water (20 ml×2) and brine (20 ml×1) successively
  9. dry with materialdried over magnesium sulfate
  10. customevaporated
  11. customto give a yellow solid
  12. customThe crude product was purified by a recycling preparative high pressure liquid chromatography
  13. customequipped with a gel permeation chromatography column (eluent: chloroform) and silica gel chromatography (eluent: hexane/ethyl acetate=1/1)

Sources & evidence

ORD record
ord-192544d56bb541bda4c6e0cdda416f7c
Source dataset
uspto-grants-2004_11
Patent number
US06826033B2

Reaction notes

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