Hydrochloric Acid → HCID 11493135, compound

HRID 1869247Notes

Reaction equation

HRID 1869247 reaction equation
[O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[N:4]([CH:11]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:12]([OH:17])[C:13]([NH:15][CH3:16])=O)[CH2:3][CH2:2]1.B.Cl>O1CCCC1>[O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[N:4]([CH:11]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:12]([OH:17])[CH2:13][NH:15][CH3:16])[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 6331BoraneHCID 68902881HCID 68902881, compound

Product 1

HCID 11493135HCID 11493135, compoundYield 98%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

A solution of (2RS,3RS)-3-(2,3-dihydro-4H-1,4-benzoxazin-4-yl)-2-hydroxy-N-methyl-3 phenylpropanamide (216 mg, 0.692 mmol) in dry tetrahydrofuran (3 mL) under nitrogen was treated dropwise with a solution of borane (1.0 M in tetrahydrofuran, 3.50 mL, 3.50 mmol), and the resulting solution was stirred at 70° C. for 2 hours. After cooling in an ice bath, the reaction mixture was treated with a 2N aqueous solution of hydrochloric acid (1 mL), and the resulting mixture was heated at 50° C. for 30 minutes. Tetrahydrofuran was removed under reduced pressure, and the aqueous residue was dissolved in water (5 mL) and washed with diethyl ether (10 mL). The aqueous layer was made alkaline with solid potassium carbonate and extracted with ethyl acetate (2×10 mL). The combined organic extracts were washed with brine, dried (sodium sulfate) and concentrated under reduced pressure to yield 202 mg (98%) (1RS,2SR)-1-(2,3-dihydro-4H-1,4-benzoxazin-4-yl)-3-(methylamino)-1-phenylpropan-2-ol as a colorless oil. This oil was dissolved in ethanol (1 mL) and treated with a solution of hydrochloric acid (0.5 mL, 4M in 1,4-dioxane). All volatiles were again removed under reduced pressure. The resulting white solid was recrystallized (minimal warm ethanol/ethyl ether/−20° C.) to yield 105 mg (41%) (1RS,2SR)-1-(2,3-dihydro-4H-1,4-benzoxazin-4-yl)-3-(methylamino)-1-phenylpropan-2-ol dihydrochloride as a white solid. MS (ESI) m/z 299.0 ([M+H]+);

Workup

  1. temperatureAfter cooling in an ice bath
  2. temperaturethe resulting mixture was heated at 50° C. for 30 minutes
  3. customTetrahydrofuran was removed under reduced pressure
  4. dissolutionthe aqueous residue was dissolved in water (5 mL)
  5. washwashed with diethyl ether (10 mL)
  6. extractionextracted with ethyl acetate (2×10 mL)
  7. washThe combined organic extracts were washed with brine
  8. dry with materialdried (sodium sulfate)
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b58a897638dc4b038de8bd2ab46878af
Source dataset
uspto-grants-2009_12
Patent number
US07638512B2

Reaction notes

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