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

HRID 75599Notes

Reaction equation

HRID 75599 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-efab74e6a8a040b1bf2855deac3f17d2
Source dataset
uspto-grants-2014_09
Patent number
US08835431B2

Reaction notes

Loading…