Ethanolamine → 5-(Hydroxy-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methyl)-6-(2,3,5-trifluoro-phenyl)-naphthalen-2-ol

HRID 1513921Notes

Reaction equation

HRID 1513921 reaction equation
C1(C(C2C=CC=CC=2)([C@H]2CCCN2)O)C=CC=CC=1.[OH:20][C:21]1[CH:22]=[C:23]2[C:28](=[CH:29][CH:30]=1)[C:27]([C:31]([C:33]1[CH:38]=[CH:37][C:36]([O:39][CH2:40][CH2:41][N:42]3[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]3)=[CH:35][CH:34]=1)=[O:32])=[C:26]([C:48]1[CH:53]=[C:52]([F:54])[CH:51]=[C:50]([F:55])[C:49]=1[F:56])[CH:25]=[CH:24]2.B.C(CN)O.[Cl-].[NH4+]>>[OH:32][CH:31]([C:33]1[CH:34]=[CH:35][C:36]([O:39][CH2:40][CH2:41][N:42]2[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]2)=[CH:37][CH:38]=1)[C:27]1[C:26]([C:48]2[CH:53]=[C:52]([F:54])[CH:51]=[C:50]([F:55])[C:49]=2[F:56])=[CH:25][CH:24]=[C:23]2[C:28]=1[CH:29]=[CH:30][C:21]([OH:20])=[CH:22]2

Participants

6

Reactant 5

HCID 700EthanolamineHCID 6331BoraneHCID 25517Ammonium ChlorideHCID 70453712-Pyrrolidinemethanol, alpha,alpha-diphenyl-, (R)-HCID 11237470[6-Hydroxy-2-(2,3,5-trifluoro-phenyl)-naphthalen-1-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanone

Product 1

HCID 670048195-(Hydroxy-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methyl)-6-(2,3,5-trifluoro-phenyl)-naphthalen-2-olYield 51%

Conditions

Temperature
45 °C

Procedure

Charge a nitrogen-purged flask with (R)-(+)-α,α-diphenyl-2-pyrrolidinemethanol (630 mg, 2.49 mmol), dissolve in 1M BH3-tetrahydrofuran (THF) (66 mL, 66 mmol) and heat to 45° C. under nitrogen. Dissolve [6-hydroxy-2-(2,3,5-trifluoro-phenyl)-naphthalen-1-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanone (8.3 g, 16.6 mmol) in THF (75 mL) and add dropwise via syringe pump to the borane solution over 2.5 hours. Add ethanolamine (20 mL, 332 mmol) slowly and heat at 45° C. for 2 hours. Pour the reaction into saturated aqueous ammonium chloride and extract twice with methylene chloride. Wash the combined organic layers with water, dry over sodium sulfate, filter and concentrate. Dissolve the residue in methylene chloride (20 mL) and allow to slowly precipitate. Collect the precipitate to yield 4.3 g (51%) of the title compound in >99% ee. Purify the mother liquor over silica gel (eluting with 1 to 6% methanol in methylene chloride) to yield 2.0 g (75% total yield) of the title compound in 91% ee. Mass spectrum (ion spray): m/z=508.3 (M+H).

Workup

  1. additionCharge a nitrogen-
  2. additionPour
  3. extractionextract twice with methylene chloride
  4. washWash the combined organic layers with water
  5. dry with materialdry over sodium sulfate
  6. filtrationfilter
  7. concentrationconcentrate
  8. dissolutionDissolve the residue in methylene chloride (20 mL)
  9. customto slowly precipitate
  10. customCollect the precipitate

Sources & evidence

ORD record
ord-d64b44e6c692415ebc753591e9213657
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

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