Triethylamine → HCID 68688740, compound

HRID 1159102Notes

Reaction equation

HRID 1159102 reaction equation
[O:1]=[S:2]1(=[O:31])[C:7]2[CH:8]=[C:9]([C:12]([F:15])([F:14])[F:13])[CH:10]=[CH:11][C:6]=2[CH2:5][CH:4]([CH2:16][N:17]([CH2:28][CH2:29]O)[C:18](=[O:27])[O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[NH:3]1.C(N(CC)CC)C.CS(OS(C)(=O)=O)(=O)=O.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>ClCCl.[Cl-].[Na+]>[F:14][C:12]([F:13])([F:15])[C:9]1[CH:10]=[CH:11][C:6]2[CH2:5][CH:4]3[CH2:16][N:17]([C:18]([O:19][CH2:20][C:21]4[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=4)=[O:27])[CH2:28][CH2:29][N:3]3[S:2](=[O:1])(=[O:31])[C:7]=2[CH:8]=1

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 81560Methanesulfonic anhydride3×HCID 2733832Lithium Hexamethyldisilazide2×HCID 69507163HCID 69507163, compound

Product 1

HCID 68688740HCID 68688740, compoundYield 83.5%

Reagents, catalysts & solvents 2

HCID 5234Sodium ChlorideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a 0° C. solution of phenylmethyl [(3,4-dihydro-1,1-dioxido-7-(trifluoromethyl)-2H-1,2-benzothiazin-3-yl)methyl](2-hydroxyethyl)carbamate (400 mg, 0.873 mmol) in dichloromethane (20 mL, dried by passage through Act I neutral alumina) was added triethylamine (0.243 mL, 1.74 mmol) and methanesulfonic anhydride (228 mg, 1.31 mmol). After 3 h, an additional 70-mg portion of methanesulfonic anhydride was added. After an additional 1 h, a 228-mg portion of methanesulfonic anhydride and a 0.243-mL portion of triethylamine were added. After 10 min, the reaction was diluted with dichloromethane (20 mL), washed with saturated sodium bicarbonate (10 mL), dried (sodium sulfate) and concentrated in vacuo. To a 0° C. solution of this residue in tetrahydrofuran (10 mL) was added, dropwise, lithium bis(trimethylsilyl)amide (1 N in tetrahydrofuran, 1.10 mL, 1.10 mmol). After 20 min, an additional 0.15-mL portion of lithium bis(trimethylsilyl)amide was added dropwise to produce an orange solution. The reaction was diluted with saturated sodium chloride (20 mL). The aqueous layer was extracted with dichloromethane (2×20 mL). The combined organic layers were dried (sodium sulfate) and concentrated in vacuo. The residue was purified by chromatography (silica, 10% ethyl acetate/hexanes to ethyl acetate gradient) to provide phenylmethyl 3,4,11,11a-tetrahydro-8-(trifluoromethyl)pyrazino[1,2-b][1,2]benzothiazine-2(1H)-carboxylate 6,6-dioxide (321 mg, 83%) as a white foam. LCMS (neg. ion spectrum) m/z 439.

Workup

  1. waitAfter an additional 1 h
  2. waitAfter 10 min
  3. washwashed with saturated sodium bicarbonate (10 mL)
  4. dry with materialdried (sodium sulfate)
  5. concentrationconcentrated in vacuo
  6. additionTo a 0° C. solution of this residue in tetrahydrofuran (10 mL) was added
  7. waitAfter 20 min
  8. customto produce an orange solution
  9. extractionThe aqueous layer was extracted with dichloromethane (2×20 mL)
  10. dry with materialThe combined organic layers were dried (sodium sulfate)
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by chromatography (silica, 10% ethyl acetate/hexanes to ethyl acetate gradient)

Sources & evidence

ORD record
ord-7fd6c3c7a41048018e164429e8363b98
Source dataset
uspto-grants-2010_10
Patent number
US07812024B2

Reaction notes

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