Acetic Acid → HCID 21072800, compound

HRID 1867345Notes

Reaction equation

HRID 1867345 reaction equation
[CH2:1]([O:8][C:9]1[C:14]2[NH:15][C:16](=[O:19])[CH2:17][O:18][C:13]=2[C:12]([C:20](=[O:26])[CH:21](OCC)O)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:27][C:28]1([CH2:31][CH2:32][N:33]2[C:38]3[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=3[C:36]([CH3:44])([CH3:43])[O:35][C:34]2=[O:45])[CH2:30][CH2:29]1.[BH4-].[Na+].C(O)(=O)C>C(O)C>[CH2:1]([O:8][C:9]1[C:14]2[NH:15][C:16](=[O:19])[CH2:17][O:18][C:13]=2[C:12]([CH:20]([OH:26])[CH2:21][NH:27][C:28]2([CH2:31][CH2:32][N:33]3[C:38]4[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=4[C:36]([CH3:43])([CH3:44])[O:35][C:34]3=[O:45])[CH2:30][CH2:29]2)=[CH:11][CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 4311764Sodium borohydrideHCID 21072805HCID 21072805, compoundHCID 21072852HCID 21072852, compound

Product 1

HCID 21072800HCID 21072800, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
50 °C

Procedure

900 mg (2.5 mmol) of 5-benzyloxy-8-(2-ethoxy-2-hydroxyacetyl)-4H-benzo[1,4]oxazin-3-one and 700 mg (2.7 mmol) of 1-[2-(1-aminocyclopropyl)ethyl]-4,4-dimethyl-1,4-dihydrobenzo[d][1,3]oxazin-2-one is dissolved in 20 mL of ethanol and stirred in each case for 30 minutes at 80° C. and 50° C. The reaction mixture is cooled, combined with 200 mg (5.3 mmol) sodium borohydride, and stirred for 2 hours at ambient temperature. Glacial acetic acid is added, the mixture is stirred for 10 minutes, and evaporated down. The residue is taken up in dichloromethane and washed successively with potassium hydrogen sulfate solution, 15% potassium carbonate solution, and sodium hydrogen carbonate solution. Then the organic phase is dried with sodium sulfate and freed from solvent. The residue is purified by column chromatography (silica gel; ethyl acetate/methanol/ammonia gradient). Recrystallization from diisopropylether. White solid. Yield: 690 mg (49%); mass spectroscopy: [M+H]+=558.

Workup

  1. temperatureThe reaction mixture is cooled
  2. stirringstirred for 2 hours at ambient temperature
  3. stirringthe mixture is stirred for 10 minutes
  4. customevaporated down
  5. washwashed successively with potassium hydrogen sulfate solution, 15% potassium carbonate solution, and sodium hydrogen carbonate solution
  6. dry with materialThen the organic phase is dried with sodium sulfate
  7. customThe residue is purified by column chromatography (silica gel; ethyl acetate/methanol/ammonia gradient)
  8. customRecrystallization from diisopropylether

Sources & evidence

ORD record
ord-931079efd227490cba0aeb7b80d32ebf
Source dataset
uspto-grants-2009_12
Patent number
US07632834B2

Reaction notes

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