Triethylamine → HCID 66673339, compound

HRID 2369202Notes

Reaction equation

HRID 2369202 reaction equation
[CH3:1][O:2][C:3](=[O:15])[C@@H:4]([CH2:8][CH:9]1[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1)[CH2:5][CH:6]=O.Cl.[NH2:17][C@H:18]1[C:27]([CH2:30][CH3:31])([CH2:28][CH3:29])[C:26]2[CH:25]=[C:24]([C:32]([NH2:34])=[O:33])[CH:23]=[CH:22][C:21]=2[CH2:20][C@@H:19]1[O:35][CH3:36].C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+].C(=O)([O-])[O-].[Na+].[Na+].S([O-])([O-])(=O)=O.[Na+].[Na+]>ClCCl.CO>[CH3:1][O:2][C:3](=[O:15])[C@@H:4]([CH2:8][CH:9]1[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1)[CH2:5][CH2:6][NH:17][C@@H:18]1[C@@H:19]([O:35][CH3:36])[CH2:20][C:21]2[C:26](=[CH:25][C:24]([C:32](=[O:33])[NH2:34])=[CH:23][CH:22]=2)[C:27]1([CH2:30][CH3:31])[CH2:28][CH3:29]

Participants

10

Reactant 7

HCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 24436Sodium SulfateHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydride2×HCID 66674010HCID 66674010, compoundHCID 86631186HCID 86631186, compound2×

Product 1

HCID 66673339HCID 66673339, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

(S)-2-cyclohexylmethyl-4-oxo-butyric acid methyl ester (822 mg, 3.38 mmol), (6S,7S)-7-amino-8,8-diethyl-6-methoxy-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid amide hydrochloride (1.01 g, 3.23 mmol) and triethylamine (326 mg, 3.23 mmol) were dissolved in dichloromethane (15 mL) and methanol (10 mL). Sodium triacetoxyborohydride (1.03 g, 4.85 mmol) was added. Over 3 h, additional sodium triacetoxyborohydride (900 mg, 4.2 mol) and (S)-2-cyclohexylmethyl-4-oxo-butyric acid methyl ester (550 mg, 2.6 mmol) were added in two portions, and the reaction mixture was stirred for 1 h after the last addition. Saturated sodium bicarbonate (60 mL) was added, and the reaction mixture was extracted with dichloromethane (4×50 mL). The organic layer was dried with Na2SO4 and concentrated. The resulting oil was dissolved in methanol (50 mL) and concentrated. The crude product was purified by preparative HPLC. Fractions containing pure product were pooled and the acetonitrile was removed at reduced pressure. Sodium carbonate (1.3 g, 12.3 mmol) was added and the product extracted into dichloromethane (3×200 mL). An additional portion of sodium sulfate (15 g, 140 mmol) was added to the aqueous layer which was extracted with dichloromethane (3×200 mL). The organic extracts were combined, dried with Na2SO4 and concentrated to give the title compound as the free base (1.16 g, 76% yield).

Workup

  1. additionafter the last addition
  2. extractionthe reaction mixture was extracted with dichloromethane (4×50 mL)
  3. dry with materialThe organic layer was dried with Na2SO4
  4. concentrationconcentrated
  5. dissolutionThe resulting oil was dissolved in methanol (50 mL)
  6. concentrationconcentrated
  7. customThe crude product was purified by preparative HPLC
  8. additionFractions containing pure product
  9. customthe acetonitrile was removed at reduced pressure
  10. extractionthe product extracted into dichloromethane (3×200 mL)
  11. extractionwas extracted with dichloromethane (3×200 mL)
  12. dry with materialdried with Na2SO4
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-9df6fb6d3dad406fb284820e2b06a82a
Source dataset
uspto-grants-2014_04
Patent number
US08703791B2

Reaction notes

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