Triethylamine → 2-[4-benzyloxy-3-(2-benzyloxyethyl)phenyl]-2-hydroxy-N-((2S)-7-hydroxy-1,2,3,4-tetrahydronaphthalen-2yl)acetamide

HRID 367344Notes

Reaction equation

HRID 367344 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]([OH:19])[C:16]([OH:18])=O)=[CH:11][C:10]=1[CH2:20][CH2:21][O:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br.[NH2:31][C@H:32]1[CH2:41][CH2:40][C:39]2[C:34](=[CH:35][C:36]([OH:42])=[CH:37][CH:38]=2)[CH2:33]1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C)C=O.O>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]([OH:19])[C:16]([NH:31][C@H:32]2[CH2:41][CH2:40][C:39]3[C:34](=[CH:35][C:36]([OH:42])=[CH:37][CH:38]=3)[CH2:33]2)=[O:18])=[CH:11][C:10]=1[CH2:20][CH2:21][O:22][CH2:23][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 232878162-[4-Benzyloxy-3-(2-benzyloxyethyl)phenyl]-2-hydroxyacetic acidHCID 69543637(S)-2-amino-7-hydroxytetralin hydrobromide

Product 1

HCID 219718242-[4-benzyloxy-3-(2-benzyloxyethyl)phenyl]-2-hydroxy-N-((2S)-7-hydroxy-1,2,3,4-tetrahydronaphthalen-2yl)acetamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

2-[4-Benzyloxy-3-(2-benzyloxyethyl)phenyl]-2-hydroxyacetic acid (1.73 g), 1.18 g of (S)-2-amino-7-hydroxytetralin hydrobromide and 1.95 g of benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate were dissolved in 11 ml of N,N-dimethylformamide, 1.23 ml of triethylamine was added to the solution with stirring at room temperature and the mixture was subjected to 3 hours of reaction. Water was added to the reaction solution and the mixture was extracted with ethyl acetate. The extract was washed with water and then dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the resulting residue was partially purified by silica gel medium pressure liquid column chromatography (eluent: hexane/ethyl acetate=1/1) to give 2-[4-benzyloxy-3-(2-benzyloxyethyl)phenyl]-2-hydroxy-N-((2S)-7-hydroxy-1,2,3,4-tetrahydronaphthalen-2yl)acetamide (diastereomer mixture). The mixture was separated by silica gel medium pressure liquid column chromatography (eluent: diethyl ether) to give 1.08 g of amorphous (-)-(2R)-2-[4-benzyloxy-3-(2-benzyloxyethyl)phenyl]-2-hydroxy-N-((2S)-7-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)acetamide (low polarity isomer) and 0.94 g of amorphous (-)-(2S)-2-[4benzyloxy-3-(2-benzyloxyethyl)phenyl]-2-hydroxy-N-((2S)-7-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)acetamide (high polarity isomer).

Workup

  1. customthe mixture was subjected to 3 hours of reaction
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe extract was washed with water
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. customthe resulting residue was partially purified by silica gel medium pressure liquid column chromatography (eluent: hexane/ethyl acetate=1/1)

Sources & evidence

ORD record
ord-32535edb4c604b2a9365072867f79079
Source dataset
uspto-grants-2000_10
Patent number
US06133266

Reaction notes

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