Hydrochloric Acid → Methyl 3,4-dihydro-2H-1,4-benzoxazine-5-carboxylate

HRID 882781Notes

Reaction equation

HRID 882781 reaction equation
B(F)(F)F.CCOCC.[CH3:10][O:11][C:12]([C:14]1[CH:15]=[CH:16][CH:17]=[C:18]2[O:23][CH2:22][C:21](=O)[NH:20][C:19]=12)=[O:13].[BH4-].[Na+].Cl.C([O-])([O-])=O.[Na+].[Na+]>C1COCC1.CCOC(C)=O>[CH3:10][O:11][C:12]([C:14]1[CH:15]=[CH:16][CH:17]=[C:18]2[O:23][CH2:22][CH2:21][NH:20][C:19]=12)=[O:13]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8000Boron trifluoride etherateHCID 10340Sodium CarbonateHCID 4311764Sodium borohydrideHCID 59153381HCID 59153381, compound

Product 1

HCID 14373654Methyl 3,4-dihydro-2H-1,4-benzoxazine-5-carboxylate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
5 °C

Procedure

Boron trifluoride diethyl etherate (7.10 mmol) is added dropwise to a mixture of 3-oxo-3,4-dihydro-2H-benzo[1,4]oxazine-5-carboxylic acid methyl ester (3.38 mmol) in THF (10 mL) to keep the temperature below 5° C. After 20 min NaBH4 (7.10 mmol) is added and the mixture is stirred at 5° C. for 90 min. EtOAc (6.0 mL) and hydrochloric acid (1.0 M, 6.0 mL) are added dropwise. The mixture is made basic by addition of aq. Na2CO3 solution, the layers are separated and the aq. layer is extracted with EtOAc. The combined organic layers are dried over MgSO4 and concentrated in vacuo to give a crude product which is purified by flash chromatography (gradient: heptane to heptane/EtOAc 3/7). LC-MS: tR=0.90 min; [M+CH3CN+H]+=235.3.

Workup

  1. customthe temperature below 5° C
  2. customthe layers are separated
  3. extractionthe aq. layer is extracted with EtOAc
  4. dry with materialThe combined organic layers are dried over MgSO4
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-413d9239e89f4d1abe4992b828c80742
Source dataset
uspto-grants-2012_08
Patent number
US08236801B2

Reaction notes

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