Trifluoroacetic acid → HCID 178487901, compound

HRID 1019911Notes

Reaction equation

HRID 1019911 reaction equation
[O:1]1[C:6]2[CH:7]=[CH:8][C:9]([CH:11]=O)=[CH:10][C:5]=2[O:4][CH2:3][CH2:2]1.FC(F)(F)C(O)=O.[NH2:20][C@H:21]1[CH2:26][CH2:25][C@H:24]([CH2:27][O:28][C:29]([C:31]2[CH:32]=[N:33][C:34]3[C:39]([CH:40]=2)=[CH:38][C:37]([O:41][CH3:42])=[CH:36][CH:35]=3)=[O:30])[CH2:23][CH2:22]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[O:1]1[C:6]2[CH:7]=[CH:8][C:9]([CH2:11][NH:20][C@H:21]3[CH2:26][CH2:25][C@H:24]([CH2:27][O:28][C:29]([C:31]4[CH:32]=[N:33][C:34]5[C:39]([CH:40]=4)=[CH:38][C:37]([O:41][CH3:42])=[CH:36][CH:35]=5)=[O:30])[CH2:23][CH2:22]3)=[CH:10][C:5]=2[O:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 2481272,3-Dihydro-1,4-benzodioxin-6-carbaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 178487900HCID 178487900, compound

Product 1

HCID 178487901HCID 178487901, compoundYield 41.6%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

2,3-Dihydro-benzo[1,4]dioxine-6-carbaldehyde (188 mg, 1.14 mmol, 1.8 eq) is added at room temperature to a stirred solution of the trifluoroacetic acid salt of 6-methoxy-quinoline-3-carboxylic acid trans-4-amino-cyclohexylmethyl ester (200 mg, 0.64 mmol, 1.0 eq) in 1,2-dichloroethane (10 mL), followed by sodium triacetoxyborohydride (1.35 g, 6.36 mmol, 10.0 eq). After 18 hours stirring at room temperature, the reaction mixture is extracted with dichloromethane (3×10 mL) and a saturated sodium hydrogen carbonate aqueous solution (10 mL). The combined organic layers are dried over sodium sulfate, filtered and concentrated to give a residue that is purified by preparative HPLC to afford 6-methoxy-quinoline-3-carboxylic acid trans-4-[(2,3-dihydro-benzo[1,4]dioxin-6-ylmethyl)-amino]-cyclohexylmethyl ester as a white powder (123 mg, 40% yield).

Workup

  1. extractionthe reaction mixture is extracted with dichloromethane (3×10 mL)
  2. dry with materialThe combined organic layers are dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give a residue that
  6. customis purified by preparative HPLC

Sources & evidence

ORD record
ord-97373572f138411687f8de86936c0722
Source dataset
uspto-grants-2014_05
Patent number
US08716280B2

Reaction notes

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