Sodium hydride → HCID 86686977, compound

HRID 630715Notes

Reaction equation

HRID 630715 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]([C:22]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)=[O:23])=[N:20][CH:21]=1>CN(C=O)C>[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]([C:22]([N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)=[O:23])=[N:20][CH:21]=2)[CH2:4][CH2:3]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 86686674(1R,4S)-4-Amino-1,2,3,4-tetrahydronaphthalen-1-olHCID 86686976HCID 86686976, compound

Product 1

HCID 86686977HCID 86686977, compoundYield 72%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
60 °C

Procedure

Intermediate A (150 mg, 0.92 mmol) was added to a suspension of sodium hydride (60% in mineral oil, 147 mg, 3.66 mmol) in DMF (3.0 mL). The reaction was stirred for 20 min, then Intermediate 17a (280 mg) in DMF (3.0 mL) was added and the reaction heated to 60° C. for 90 min. The mixture was cooled and quenched by dropwise addition of MeOH. The solution was diluted with MeOH and loaded onto an SCX-2 cartridge, which was washed sequentially with MeOH and 2M NH3 in MeOH. The basic fractions were evaporated in vacuo then purified by FCC, using 0-10% [2M NH3 in MeOH] in DCM, to give the title compound (234 mg, 0.66 mmol, 72%). LCMS (Method 4): Rt 1.60 min, m/z 354 [MH+].

Workup

  1. temperatureThe mixture was cooled
  2. customquenched by dropwise addition of MeOH
  3. additionThe solution was diluted with MeOH
  4. washwas washed sequentially with MeOH and 2M NH3 in MeOH
  5. customThe basic fractions were evaporated in vacuo
  6. customthen purified by FCC

Sources & evidence

ORD record
ord-6b504f50613d459b951b5164d62b4e2d
Source dataset
uspto-grants-2016_04
Patent number
US09315503B2

Reaction notes

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