Dichloromethane → HCID 11703849, compound

HRID 12118Notes

Reaction equation

HRID 12118 reaction equation
C([O:8][C:9]1[CH:10]=[C:11]([C:20](=[O:26])[CH:21](OCC)O)[C:12]2[O:17][CH2:16][C:15](=[O:18])[NH:14][C:13]=2[CH:19]=1)C1C=CC=CC=1.[F:27][C:28]1[CH:29]=[C:30]([CH2:35][C:36]([NH2:39])([CH3:38])[CH3:37])[CH:31]=[CH:32][C:33]=1[F:34].[BH4-].[Li+].ClCCl>O1CCCC1.O>[F:27][C:28]1[CH:29]=[C:30]([CH2:35][C:36]([NH:39][CH2:21][CH:20]([C:11]2[C:12]3[O:17][CH2:16][C:15](=[O:18])[NH:14][C:13]=3[CH:19]=[C:9]([OH:8])[CH:10]=2)[OH:26])([CH3:37])[CH3:38])[CH:31]=[CH:32][C:33]=1[F:34]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 4148881Lithium borohydrideHCID 22063467HCID 22063467, compoundHCID 22063474HCID 22063474, compound

Product 1

HCID 11703849HCID 11703849, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

357 mg (1 mmol) of 6-benzyloxy-8-(2-ethoxy-2-hydroxy-acetyl)-4H-benzo[1,4]oxazin-3-one and 185 mg (1 mmol) of 2-(3,4-difluorophenyl)-1,1-dimethylethylamine are stirred for 30 minutes in 5 mL tetrahydrofuran at ambient temperature. It is cooled to 0° C. and, under an argon atmosphere, 1.5 mL of a 2 molar solution of lithium borohydride in tetrahydrofuran is added dropwise. The mixture is stirred for 30 minutes at ambient temperature, combined with 10 mL dichloromethane, and 3 mL water, stirred for a further hour and then filtered through an EXTRELUT® column. The eluate containing the ethanol amine is freed from solvent. The residue is dissolved in methanol and hydrogenated with palladium on charcoal (10%) as catalyst at 2.5 bar and ambient temperature. Then the catalyst is separated off and the crude product is purified by chromatography. White solid. Yield: 31 mg (6%, trifluoroethyl acetate); mass spectroscopy: [M+H]+=393.

Workup

  1. stirringstirred for a further hour
  2. filtrationfiltered through an EXTRELUT® column
  3. additionThe eluate containing the ethanol amine
  4. dissolutionThe residue is dissolved in methanol and hydrogenated with palladium on charcoal (10%) as catalyst at 2.5 bar and ambient temperature
  5. customThen the catalyst is separated off
  6. customthe crude product is purified by chromatography

Sources & evidence

ORD record
ord-4441e79696ac40c1bf0f8abad85e67ee
Source dataset
uspto-grants-2010_06
Patent number
US07727984B2

Reaction notes

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