3'-({[(1,1-Dimethylethyl)(dimethyl)silyl]oxy}methyl)-2-fluoro-3-biphenylcarboxamide → [3'-(Aminomethyl)-2'-fluoro-3-biphenylyl]methanol

HRID 564475Notes

Reaction equation

HRID 564475 reaction equation
CC([Si](C)(C)[O:6][CH2:7][C:8]1[CH:9]=[C:10]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([NH2:22])=O)[C:15]=2[F:23])[CH:11]=[CH:12][CH:13]=1)(C)C>C1COCC1>[NH2:22][CH2:20][C:16]1[C:15]([F:23])=[C:14]([C:10]2[CH:11]=[CH:12][CH:13]=[C:8]([CH2:7][OH:6])[CH:9]=2)[CH:19]=[CH:18][CH:17]=1

Participants

3

Reactant 1

HCID 578133053'-({[(1,1-Dimethylethyl)(dimethyl)silyl]oxy}methyl)-2-fluoro-3-biphenylcarboxamide

Product 1

HCID 57813385[3'-(Aminomethyl)-2'-fluoro-3-biphenylyl]methanolYield 33.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 3′-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)-2-fluoro-3-biphenylcarboxamide (3.8 g, 10.6 mmol) in THF (40 mL) which was cooled to 0° C., BH3Me2S (14.0 mL, 21.2 mmol) was added dropwise. Then the reaction was stirred at 50° C. overnight. The reaction was quenched by adding HCl (10 mL, 3 N) and the result mixture was stirred for 2 h before THF was removed under vacuum. The aqueous layer was extracted with AcOEt (30 mL) then the pH was adjusted to around 9.0 by adding Na2CO3. The aqueous layer was extracted with AcOEt (50 mL×2), and dried over Na2SO4. After the solvent was removed, the crude product was purified on Al2O3 column chromatography, eluting with CH2Cl2/EA (10:1). 0.83 g of the product, [3′-(aminomethyl)-2′-fluoro-3-biphenylyl]methanol, was obtained (yield: 33%). 1H NMR (400 MHz, DMSO): δ 3.80 (s, 2 H), 4.56 (s, 2 H), 7.23-7.51 (m, 7 H); 13C NMR (400 MHz, DMSO): δ 62.8, 124.3, 125.8, 126.9, 127.2, 128.0, 128.1, 128.3, 128.4, 128.6, 131.6, 131.8, 135.6, 142.9, 155.6, 158.1; HPLC: retention time: 4.053 min; purity: 98.6% (HPLC).

Workup

  1. additionBH3Me2S (14.0 mL, 21.2 mmol) was added dropwise
  2. customThe reaction was quenched
  3. additionby adding HCl (10 mL, 3 N)
  4. stirringthe result mixture was stirred for 2 h before THF
  5. customwas removed under vacuum
  6. extractionThe aqueous layer was extracted with AcOEt (30 mL)
  7. additionby adding Na2CO3
  8. extractionThe aqueous layer was extracted with AcOEt (50 mL×2)
  9. dry with materialdried over Na2SO4
  10. customAfter the solvent was removed
  11. customthe crude product was purified on Al2O3 column chromatography
  12. washeluting with CH2Cl2/EA (10:1)

Sources & evidence

ORD record
ord-66addf4895b542a2b458496cc4fb89fb
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

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