Sodium hydride → HCID 86687096, compound

HRID 1402242Notes

Reaction equation

HRID 1402242 reaction equation
[NH2:1][C@@H:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C@H:5]([OH:12])[CH2:4][CH2:3]1.[H-].[Na+].F[C:16]1[CH:17]=[CH:18][C:19]2[N:20]([C:22]([N:25]3[CH2:30][CH2:29][CH2:28][C@@H:27]([CH2:31][O:32][Si:33]([CH:40]([CH3:42])[CH3:41])([CH:37]([CH3:39])[CH3:38])[CH:34]([CH3:36])[CH3:35])[CH2:26]3)=[N:23][N:24]=2)[CH:21]=1>CN(C=O)C>[CH:40]([Si:33]([CH:34]([CH3:36])[CH3:35])([CH:37]([CH3:39])[CH3:38])[O:32][CH2:31][C@@H:27]1[CH2:28][CH2:29][CH2:30][N:25]([C:22]2[N:20]3[CH:21]=[C:16]([O:12][C@H:5]4[C:6]5[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=5)[C@@H:2]([NH2:1])[CH2:3][CH2:4]4)[CH:17]=[CH:18][C:19]3=[N:24][N:23]=2)[CH2:26]1)([CH3:41])[CH3:42]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 86686674(1R,4S)-4-Amino-1,2,3,4-tetrahydronaphthalen-1-olHCID 86687095HCID 86687095, compound

Product 1

HCID 86687096HCID 86687096, compoundYield 57.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of Intermediate A (140 mg, 0.860 mmol) in dry DMF (2 mL) at RT under Ar was added NaH (60% dispersion in oil, 49.0 mg, 1.23 mmol) (CARE: gas evolution) and the resulting brown suspension was stirred at RT for 45 min. A solution of Intermediate 77b (333 mg, 0.819 mmol) in dry DMF (2 mL) was added and the resulting dark brown solution stirred at 60° C. under Ar for 2.5 h. The solution was concentrated in vacuo, redissolved in MeOH (2 mL) and AcOH (0.100 mL), then applied to and SCX-2 cartridge, and washed with MeOH (100 ml). The product was eluted with 2M NH3 in MeOH (75 mL); concentration in vacuo left a viscous dark brown oil. FCC, using 2-7% [2M NH3 in MeOH] in DCM, gave the title compound as a yellow-brown viscous oil (257 mg, 57%). LCMS (Method 3): Rt 3.27 min, m/z 550 [MH+].

Workup

  1. stirringthe resulting dark brown solution stirred at 60° C. under Ar for 2.5 h
  2. concentrationThe solution was concentrated in vacuo
  3. dissolutionredissolved in MeOH (2 mL)
  4. washwashed with MeOH (100 ml)
  5. washThe product was eluted with 2M NH3 in MeOH (75 mL)
  6. concentrationconcentration in vacuo
  7. waitleft a viscous dark brown oil

Sources & evidence

ORD record
ord-970780b3b2394391ae41993798b7f43b
Source dataset
uspto-grants-2014_12
Patent number
US08907094B2

Reaction notes

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