Ethyl Acetate → HCID 69507163, compound

HRID 1159101Notes

Reaction equation

HRID 1159101 reaction equation
[OH:1][CH2:2][CH2:3][NH:4][CH2:5][CH:6]1[CH2:11][C:10]2[CH:12]=[CH:13][C:14]([C:16]([F:19])([F:18])[F:17])=[CH:15][C:9]=2[S:8](=[O:21])(=[O:20])[NH:7]1.C(=O)([O-])[O-].[Na+].[Na+].Cl[C:29]([O:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)=[O:30].C(OCC)(=O)C>O1CCCC1>[O:21]=[S:8]1(=[O:20])[C:9]2[CH:15]=[C:14]([C:16]([F:18])([F:17])[F:19])[CH:13]=[CH:12][C:10]=2[CH2:11][CH:6]([CH2:5][N:4]([CH2:3][CH2:2][OH:1])[C:29](=[O:30])[O:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[NH:7]1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 10387Benzyl chloroformateHCID 68686374HCID 68686374, compound

Product 1

HCID 69507163HCID 69507163, compoundYield 51.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3,4-dihydro-N-(2-hydroxyethyl)-7-(trifluoromethyl)-2H-1,2-benzothiazine-3-methanamine 1,1-dioxide (124 mg, 0.382 mmol) in tetrahydrofuran (4 mL) was added, sequentially, 0.5 N aqueous sodium carbonate (2 mL, 1 mmol) and benzyl chloroformate (0.066 mL, 0.46 mmol). The reaction was stirred for 25 min. The layers were separated and the aqueous layer was extracted with dichloromethane (5 mL). The combined organic layers were washed with saturated sodium chloride (5 mL) and were concentrated in vacuo. To the residue taken up in methanol (5 mL) was added 2 N potassium hydroxide (0.5 mL). After 15 min, the reaction was brought to pH 4 with 1 N HCl. The reaction was concentrated in vacuo to remove the methanol. The residue was partitioned between dichloromethane (10 mL) and water (5 mL). The organic layer was dried (magnesium sulfate) and concentrated in vacuo to provide a yellow oil. Chromatography of this residue (silica, 30% ethyl acetate/hexanes to ethyl acetate gradient) provided 90 mg (51%) of a phenylmethyl [(3,4-dihydro-1,1-dioxido-7-(trifluoromethyl)-2H-1,2-benzothiazin-3-yl)methyl](2-hydroxyethyl)carbamate as a white solid: LCMS (neg. ion spectrum) m/z 457.

Workup

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted with dichloromethane (5 mL)
  3. washThe combined organic layers were washed with saturated sodium chloride (5 mL)
  4. concentrationwere concentrated in vacuo
  5. additionwas added 2 N potassium hydroxide (0.5 mL)
  6. waitAfter 15 min
  7. concentrationThe reaction was concentrated in vacuo
  8. customto remove the methanol
  9. customThe residue was partitioned between dichloromethane (10 mL) and water (5 mL)
  10. dry with materialThe organic layer was dried (magnesium sulfate)
  11. concentrationconcentrated in vacuo
  12. customto provide a yellow oil

Sources & evidence

ORD record
ord-3f3b1a2db9594926a05678beb4963a36
Source dataset
uspto-grants-2010_10
Patent number
US07812024B2

Reaction notes

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