Hydrochloric Acid → HCID 67071612, compound

HRID 1260562Notes

Reaction equation

HRID 1260562 reaction equation
B.[CH:2]([O:5][C:6]1[N:11]=[CH:10][C:9]([O:12][C:13]2[CH:18]=[CH:17][C:16]([CH2:19][CH2:20][C@H:21]([NH2:25])[CH:22]([CH3:24])[CH3:23])=[CH:15][CH:14]=2)=[CH:8][CH:7]=1)([CH3:4])[CH3:3].C1COCC1.C(ON=C(C(C)C)CCC1C=CC(OC2C=NC(OC(C)C)=CC=2)=CC=1)C1C=CC=CC=1.O1CCOB1OC(C1C=CC=CC=1)(C1C=CC=CC=1)[C@@H](N)C(C)C.B.C1COCC1.Cl.[OH-].[Na+]>C1COCC1>[CH:2]([O:5][C:6]1[N:11]=[CH:10][C:9]([O:12][C:13]2[CH:18]=[CH:17][C:16]([CH2:19][CH2:20][C@@H:21]([NH2:25])[CH:22]([CH3:24])[CH3:23])=[CH:15][CH:14]=2)=[CH:8][CH:7]=1)([CH3:4])[CH3:3]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 2723981Borane;tetrahydrofuranHCID 25051993(2S)-1-[(1,3,2-Dioxaborolan-2-yl)oxy]-3-methyl-1,1-diphenylbutan-2-amineHCID 86656071HCID 86656071, compoundHCID 178419154HCID 178419154, compound

Product 1

HCID 67071612HCID 67071612, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(S)-1-{2-[4-(6-isopropoxypyridin-3-yloxy)phenyl]ethyl}-2-methylpropylamine Borane-THF (2.87 ml, 2.87 mmol) is added dropwise under argon at 0° C. to 1-[4-(6-isopropoxypyridin-3-yloxy)phenyl]-4-methylpentan-3-one O-benzyloxime (310 mg, 0.717 mmol) in 15 ml of anhydrous THF. Then, (S)-1-[([1,3,2]dioxaborolan-2-yloxy)-diphenylmethyl]-2-methylpropylamine (23.3 mg) is added and the mixture is stirred for 2 days. Following addition of twice 1.5 ml of borane-THF stirring is continued for 4 h each time. % N hydrochloric acid is carefully added for hydrolysis, the mixture is rendered alkaline with aqueous sodium hydroxide solution and extracted with ethyl acetate. The organic phase is separated off, concentrated and purified by preparative HPLC (PR18, acetonitrile/water 0.1% TFA). Yield: 160 mg (68%), M+H+: 329.3. Chiral chromatography is performed (Chiralcel OD-H, heptane:ethanol=5:1+0.1% DEA) to obtain the enantiomers (R)-1-{2-[4-(6-isopropoxypyridin-3-yloxy)phenyl]ethyl}-2-methylpropylamine (RF: 4.442 min), Yield: 49 mg (21%), M+H+: 329.3. (S)-1-{2-[4-(6-Isopropoxypyridin-3-yloxy)phenyl]ethyl}-2-methylpropylamine (RF: 5.965 min), Yield: 50 mg (21%), M+H+: 329.3.

Workup

  1. waitis continued for 4 h
  2. extractionextracted with ethyl acetate
  3. customThe organic phase is separated off
  4. concentrationconcentrated
  5. custompurified by preparative HPLC (PR18, acetonitrile/water 0.1% TFA)

Sources & evidence

ORD record
ord-96c6a3a28b294cabaff25d835c8740fa
Source dataset
uspto-grants-2013_06
Patent number
US08470841B2

Reaction notes

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