Triethylamine → (-)-(2R)-2-(2,2-dimethylbenzo[1,2-d]-1,3-dioxan-6-yl)-2-hydroxy-N-((2S)-7-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)acetamide

HRID 367333Notes

Reaction equation

HRID 367333 reaction equation
[CH3:1][C:2]1([CH3:17])[O:7][C:6]2[CH:8]=[CH:9][C:10]([C@@H:12]([OH:16])[C:13]([OH:15])=O)=[CH:11][C:5]=2[CH2:4][O:3]1.Br.[NH2:19][C@H:20]1[CH2:29][CH2:28][C:27]2[C:22](=[CH:23][C:24]([OH:30])=[CH:25][CH:26]=2)[CH2:21]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>[CH3:17][C:2]1([CH3:1])[O:7][C:6]2[CH:8]=[CH:9][C:10]([C@@H:12]([OH:16])[C:13]([NH:19][C@H:20]3[CH2:29][CH2:28][C:27]4[C:22](=[CH:23][C:24]([OH:30])=[CH:25][CH:26]=4)[CH2:21]3)=[O:15])=[CH:11][C:5]=2[CH2:4][O:3]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 69543637(S)-2-amino-7-hydroxytetralin hydrobromideHCID 70135960(-)-(R)-2-(2,2-Dimethylbenzo[1,2-d]-1,3-dioxan-6-yl)2-hydroxyacetic acid

Product 1

HCID 70136692(-)-(2R)-2-(2,2-dimethylbenzo[1,2-d]-1,3-dioxan-6-yl)-2-hydroxy-N-((2S)-7-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)acetamideYield 88.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

(-)-(R)-2-(2,2-Dimethylbenzo[1,2-d]-1,3-dioxan-6-yl)2-hydroxyacetic acid (130 mg), 148 mg of (S)-2-amino-7-hydroxytetralin hydrobromide and 243 mg of benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate were dissolved in 1.4 ml of N,N-dimethylformamide, 0.15 ml of triethylamine was added to the solution with stirring under ice-cooling, and the mixture was subjected to 15 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 dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the resulting residue was purified by aminopropylated silica gel medium pressure liquid column chromatography (eluent: ethyl acetate/acetone=4/1) and then recrystallized from ethyl acetate to give 186 mg of (-)-(2R)-2-(2,2-dimethylbenzo[1,2-d]-1,3-dioxan-6-yl)-2-hydroxy-N-((2S)-7-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)acetamide having a melting point of 169 to 170° C.

Workup

  1. temperaturecooling
  2. customthe mixture was subjected to 15 hours of reaction
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe extract was washed with water
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe solvent was evaporated under reduced pressure
  7. customthe resulting residue was purified by aminopropylated silica gel medium pressure liquid column chromatography (eluent: ethyl acetate/acetone=4/1)
  8. customrecrystallized from ethyl acetate

Sources & evidence

ORD record
ord-2fd58907ba894939abf035bdf4ce48e1
Source dataset
uspto-grants-2000_10
Patent number
US06133266

Reaction notes

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