Sodium Carbonate → HCID 11553707, compound

HRID 600752Notes

Reaction equation

HRID 600752 reaction equation
[CH2:1]([C:3]1([CH2:13][C:14]([CH:20]=[N:21][C:22]2[CH:31]=[CH:30][CH:29]=[C:28]3[C:23]=2[CH:24]=[CH:25][N:26]=[CH:27]3)([OH:19])[C:15]([F:18])([F:17])[F:16])[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH2:6][CH2:5][CH2:4]1)[CH3:2].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])[O-].[Na+].[Na+]>C(O)(=O)C>[CH2:1]([C:3]1([CH2:13][C:14]([CH2:20][NH:21][C:22]2[CH:31]=[CH:30][CH:29]=[C:28]3[C:23]=2[CH:24]=[CH:25][N:26]=[CH:27]3)([OH:19])[C:15]([F:16])([F:17])[F:18])[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH2:6][CH2:5][CH2:4]1)[CH3:2]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 5049666Sodium triacetoxyborohydride2×HCID 24749156HCID 24749156, compound2×

Product 1

HCID 11553707HCID 11553707, compound

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a solution of 3-(1-ethyl-1,2,3,4-tetrahydro-1-naphthalenyl)-1,1,1-trifluoro-2-[(5-isoquinolinylimino) methyl]-2-propanol (Intermediate 18) (185 mg, 0.43 mmol) in glacial acetic acid (5 ml) stirred under nitrogen at room temperature, was added sodium triacetoxyborohydride (276 mg, 1.3 mmol) and the solution was stirred for approximately 4 h. Further sodium triacetoxyborohydride (100 mg, 0.47 mmol) was added and the reaction was stirred for 1 h. The solution was then carefully added to saturated aqueous sodium carbonate and when effervescence had ceased was extracted into ethyl acetate (×2). The combined organic layers were washed successively with saturated aqueous sodium carbonate solution, water and finally brine/water (1:1), passed through a hydrophobic frit and evaporated in vacuo to yield a pale yellow oil. The crude product was purified on a 10 g silica SPE cartridge eluting with a 0-100% dichloromethane in heptane gradient followed by 1% methanol in dichloromethane. This gave, in order of elution, Example 4-D2 (racemic diastereomer 2) (45 mg) and Example 4-D1 (racemic diastereomer 1) (35 mg).

Workup

  1. stirringthe reaction was stirred for 1 h
  2. extractionhad ceased was extracted into ethyl acetate (×2)
  3. washThe combined organic layers were washed successively with saturated aqueous sodium carbonate solution, water and finally brine/water (1:1)
  4. customevaporated in vacuo
  5. customto yield a pale yellow oil
  6. customThe crude product was purified on a 10 g silica SPE cartridge
  7. washeluting with a 0-100% dichloromethane in heptane gradient

Sources & evidence

ORD record
ord-be0999fa8c4741ce91441819a1b028aa
Source dataset
uspto-grants-2011_03
Patent number
US07902224B2

Reaction notes

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