Ethanolamine → 5-{[4-(2-Azepan-1-yl-ethoxy)-phenyl]-hydroxy-methyl}-6-(2,4,6-trifluoro-phenyl)-naphthalen-2-ol

HRID 1513972Notes

Reaction equation

HRID 1513972 reaction equation
B.C1CN[C@H](C(O)(C2C=CC=CC=2)C2C=CC=CC=2)C1.[N:21]1([CH2:28][CH2:29][O:30][C:31]2[CH:36]=[CH:35][C:34]([C:37]([C:39]3[C:48]4[C:43](=[CH:44][C:45]([OH:49])=[CH:46][CH:47]=4)[CH:42]=[CH:41][C:40]=3[C:50]3[C:55]([F:56])=[CH:54][C:53]([F:57])=[CH:52][C:51]=3[F:58])=[O:38])=[CH:33][CH:32]=2)[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1.C(CN)O>C1COCC1.[Cl-].[Na+].O>[N:21]1([CH2:28][CH2:29][O:30][C:31]2[CH:36]=[CH:35][C:34]([CH:37]([OH:38])[C:39]3[C:40]([C:50]4[C:55]([F:56])=[CH:54][C:53]([F:57])=[CH:52][C:51]=4[F:58])=[CH:41][CH:42]=[C:43]4[C:48]=3[CH:47]=[CH:46][C:45]([OH:49])=[CH:44]4)=[CH:33][CH:32]=2)[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1

Participants

7

Reactant 4

HCID 700EthanolamineHCID 6331BoraneHCID 27248992-Pyrrolidinemethanol, alpha,alpha-diphenyl-, (S)-HCID 67004267[4-(2-Azepan-1-yl-ethoxy)-phenyl]-[6-hydroxy-2-(2,4,6-trifluoro-phenyl)naphthalen-1-yl]-methanone

Product 1

HCID 670049855-{[4-(2-Azepan-1-yl-ethoxy)-phenyl]-hydroxy-methyl}-6-(2,4,6-trifluoro-phenyl)-naphthalen-2-olYield 88%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
45 °C

Procedure

Charge a flask with 1M borane in THF (4 mL) and (R)-(+) α,α-diphenylprolinol (26 mg, 0.1 mmol). Dissolve [4-(2-azepan-1-yl-ethoxy)-phenyl]-[6-hydroxy-2-(2,4,6-trifluoro-phenyl)-naphthalen-1-yl]-methanone (348 mg, 0.7 mmol) in THF (3 mL) and add to the catalyst solution via syringe pump over 1.5 hours at 45° C. Upon completion of the reaction add ethanolamine (0.8 mL, 13.4 mmol) and heat at 45° C. for 2 hours. Cool the reaction to room temperature and add brine (5 mL) and stir for 1 hour. Filter the reaction and separate layers. Dry the organic layer with sodium sulfate, filter and concentrate in vacuo. Purify by silica gel chromatography using a 1.5-5% gradient of methanol in dichloromethane to yield 306 mg (88%) of the title compound: mass spectrum (ion spray) m/z=522 (M+H).

Workup

  1. temperatureCool
  2. customthe reaction to room temperature
  3. filtrationFilter
  4. customthe reaction
  5. customseparate layers
  6. dry with materialDry the organic layer with sodium sulfate
  7. filtrationfilter
  8. concentrationconcentrate in vacuo
  9. customPurify by silica gel chromatography

Sources & evidence

ORD record
ord-f82e2217949f4c9fb29cb26aec1f8ea0
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

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