Sodium hydride → HCID 86687164, compound

HRID 1402323Notes

Reaction equation

HRID 1402323 reaction equation
[H-].[Na+].[NH2:3][C@@H:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C@H:7]([OH:14])[CH2:6][CH2:5]1.[CH2:15]([N:18]([CH2:29][CH:30]=[CH2:31])[C:19]1[N:23]2[CH:24]=[C:25](F)[CH:26]=[CH:27][C:22]2=[N:21][N:20]=1)[CH:16]=[CH2:17]>CN(C=O)C>[NH2:3][C@@H:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C@H:7]([O:14][C:25]2[CH:26]=[CH:27][C:22]3[N:23]([C:19]([N:18](/[CH:29]=[CH:30]/[CH3:31])/[CH:15]=[CH:16]/[CH3:17])=[N:20][N:21]=3)[CH:24]=2)[CH2:6][CH2:5]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 86686674(1R,4S)-4-Amino-1,2,3,4-tetrahydronaphthalen-1-olHCID 86687163HCID 86687163, compound

Product 1

HCID 86687164HCID 86687164, compoundYield 61.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a suspension of sodium hydride (40% in mineral oil, 690 mg, 17.31 mmol) in DMF (20 mL) was added Intermediate A (1.12 g, 6.92 mmol) and the reaction mixture was stirred for 20 min at RT. A solution of Intermediate 101b (1.34 g, 5.77 mmol) in DMF (20 mL) was added and the reaction mixture was stirred at RT for 1 h. The reaction mixture was quenched by careful addition of MeOH and then loaded onto an SCX cartridge. The cartridge was washed with MeOH and the product eluted with 2M NH3 in MeOH. The product containing fractions were concentrated in vacuo and the resultant residue was purified by FCC on silica, using a gradient of 0-10% [2M NH3 in MeOH] in DCM, to give the title compound (1.33 g, 61%) as an orange gum. 1H NMR (400 MHz, CDCl3): 0.92-1.13 (1H, m), 1.39 (6H, dd, J=7.2, 1.7 Hz), 1.82-2.16 (4H, m), 2.26-2.38 (1H, m), 3.93-3.99 (1H, m), 4.99-5.10 (2H, m), 5.18 (1H, t, J=4.4 Hz), 6.10 (2H, dd, J=8.2, 2.0 Hz), 7.09 (1H, dd, J=9.9, 2.2 Hz), 7.25-7.44 (3H, m), 7.48-7.53 (1H, m), 7.57-7.66 (2H, m).

Workup

  1. stirringthe reaction mixture was stirred at RT for 1 h
  2. customThe reaction mixture was quenched by careful addition of MeOH
  3. washThe cartridge was washed with MeOH
  4. washthe product eluted with 2M NH3 in MeOH
  5. additionThe product containing fractions
  6. concentrationwere concentrated in vacuo
  7. customthe resultant residue was purified by FCC on silica

Sources & evidence

ORD record
ord-161e0ca8da2d46afa46566223aff575b
Source dataset
uspto-grants-2014_12
Patent number
US08907094B2

Reaction notes

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