Sodium Hydroxide → (1R,4S)-4-Amino-6-fluoro-1,2,3,4-tetrahydro-naphthalen-1-ol

HRID 572089Notes

Reaction equation

HRID 572089 reaction equation
FC(F)(F)C([NH:5][C@@H:6]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([F:16])[CH:14]=2)[C@H:9]([OH:17])[CH2:8][CH2:7]1)=O.[OH-].[Na+]>CO.O>[NH2:5][C@@H:6]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([F:16])[CH:14]=2)[C@H:9]([OH:17])[CH2:8][CH2:7]1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 86686697HCID 86686697, compound

Product 1

HCID 86686696(1R,4S)-4-Amino-6-fluoro-1,2,3,4-tetrahydro-naphthalen-1-olYield 86%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a solution of 2,2,2-trifluoro-N-((1S,4R)-7-fluoro-4-hydroxy-1,2,3,4-tetrahydro-naphthalen-1-yl)-acetamide (synthesised in an analogous manner to that described in WO 2009/048474, which is incorporated herein by reference in its entirety) (2.31 g, 8.34 mmol) in MeOH (22.5 mL), was added a solution of sodium hydroxide (0.834 g, 20.8 mmol) in water (15 mL) and the mixture was stirred at RT for 65 h. The mixture was concentrated in vacuo, then applied to an SCX-2 cartridge (50 g), washing with methanol then eluting basic components with 0.2-1 M ammonia in methanol. Product containing fractions were combined and concentrated in vacuo. The residue was purified by FCC, using 0-10% [2M NH3 in MeOH] in DCM, to give the title compound (1.29 g, 86%). 1H NMR (300 MHz, d6-DMSO): 1.60-2.15 (6H, m), 3.62-3.71 (1H, m), 4.49 (1H, t, J 4.7), 5.15 (1H, br s), 6.98 (1H, dt, J 8.6, 2.8), 7.28 (1H, dd, J 10.7, 2.8), 7.36 (1H, dd, J 8.6, 6.2).

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. washwashing with methanol
  3. washthen eluting basic components with 0.2-1 M ammonia in methanol
  4. additionProduct containing fractions
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by FCC

Sources & evidence

ORD record
ord-d0d48cc9a7ba4af4ace52416c31654b4
Source dataset
uspto-grants-2015_05
Patent number
US09029373B2

Reaction notes

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