Sodium hydride → HCID 86686990, compound

HRID 2282401Notes

Reaction equation

HRID 2282401 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]([CH3:39])[CH2:26][CH2:27][O:28][Si:29]([CH:36]([CH3:38])[CH3:37])([CH:33]([CH3:35])[CH3:34])[CH:30]([CH3:32])[CH3:31])=[N:23][N:24]=2)[CH:21]=1.[NH4+].[Cl-]>CN(C=O)C.O>[NH2:1][C@@H:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C@H:5]([O:12][C:16]2[CH:17]=[CH:18][C:19]3[N:20]([C:22]([N:25]([CH3:39])[CH2:26][CH2:27][O:28][Si:29]([CH:33]([CH3:35])[CH3:34])([CH:30]([CH3:32])[CH3:31])[CH:36]([CH3:37])[CH3:38])=[N:23][N:24]=3)[CH:21]=2)[CH2:4][CH2:3]1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 86686674(1R,4S)-4-Amino-1,2,3,4-tetrahydronaphthalen-1-olHCID 86686991HCID 86686991, compound

Product 1

HCID 86686990HCID 86686990, compoundYield 29%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Intermediate A (93 mg, 0.568 mmol) was added dropwise to a suspension of NaH (60% dispersion in oil, 68 mg, 1.71 mmol) in DMF (3 mL) at RT under N2. The mixture was stirred for 15 min then Intermediate 25b (160 mg, 0.437 mmol) was added and the mixture stirred at 60° C. under N2 for 3 h. Sat. aq. NH4Cl solution (0.2 mL) was added to the cooled mixture which was then diluted with water (15 mL) and extracted with EtOAc (3×15 mL). The combined organics were washed with brine (15 mL) and dried (Na2SO4). The solvent was evaporated, the residue applied to an SCX-2 cartridge and washed with MeOH. The product was eluted with 2M NH3 in MeOH; concentration in vacuo left a brown foam. FCC, using 0-6% [2M NH3 in MeOH] in DCM, gave the title compound (64 mg, 29%). LCMS (Method 1): Rt 2.71 min, m/z 510 [MH+].

Workup

  1. stirringthe mixture stirred at 60° C. under N2 for 3 h
  2. extractionextracted with EtOAc (3×15 mL)
  3. washThe combined organics were washed with brine (15 mL)
  4. dry with materialdried (Na2SO4)
  5. customThe solvent was evaporated
  6. washwashed with MeOH
  7. washThe product was eluted with 2M NH3 in MeOH
  8. concentrationconcentration in vacuo
  9. waitleft a brown foam

Sources & evidence

ORD record
ord-009a82fd62174ca0ae648b206f4ffb8b
Source dataset
uspto-grants-2015_09
Patent number
US09139584B2

Reaction notes

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