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

HRID 657352Notes

Reaction equation

HRID 657352 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%

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 mixture 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 chomatography, eluting with CH2Cl2/EA (10:1). [3′-(aminomethyl)-2′-fluoro-3-biphenylyl]methanol was obtained (0.83 g, yield: 33%). 1H NMR (400 MHz, DMSO) δ 3.80 (s, 2H), 4.56 (s, 2H), 7.23-7.51 (m, 7H); 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 mixture 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 chomatography
  12. washeluting with CH2Cl2/EA (10:1)

Sources & evidence

ORD record
ord-ef49069e334841f8920b2c92806a2567
Source dataset
uspto-grants-2011_12
Patent number
US08071588B2

Reaction notes

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