Hydrochloric Acid → (Hexahydro-5-oxo-1,4-thiazepin-6-yl)carbamic acid, (1,1-dimethylethyl) ester

HRID 1462485Notes

Reaction equation

HRID 1462485 reaction equation
[NH2:1][CH2:2][CH2:3][S:4][CH2:5][C@@H:6]([C:15]([O:17]C)=O)[NH:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9].[OH-].[Na+].Cl.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1>C(OCC)(=O)C.O1CCOCC1>[O:17]=[C:15]1[CH:6]([NH:7][C:8](=[O:9])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH2:5][S:4][CH2:3][CH2:2][NH:1]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 199401P,P-Diphenylphosphinic azideHCID 131713584HCID 131713584, compound

Product 1

HCID 15591256(Hexahydro-5-oxo-1,4-thiazepin-6-yl)carbamic acid, (1,1-dimethylethyl) ester

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of S-(2-aminoethyl)-N-[(1,1-dimethylethoxy)carbonyl]-L-cysteine, methyl ester (7.5 g., 26.9 mmole), 1N sodium hydroxide (31.0 ml., 1.15 eq.), and dioxane (30 ml.) is stirred at room temperature for 2 hours. The reaction is then treated with 1N hydrochloric acid (4.1 ml.) to quench excess hydroxide. The dioxane and water are evaporated and the residual water is removed azeotropically with acetonitrile (twice). The resulting foam is taken into dry dimethylformamide (100 ml.), treated with diphenylphosphoryl azide (6.5 ml., 1.1 eq.), and stirred under argon at 25° for 3.5 days. The reaction mixture is diluted with ethyl acetate and washed successively with water, saturated sodium bicarbonate, 5% potassium bisulfate, brine, dried (MgSO4), and evaporated. The residue (3.0 g.) is taken up in hot ethyl acetate and upon cooling 1.1 g. of the product crystallizes as a colorless solid. The mother liquor (1.9 g.) is chromatographed on silica (70 g.) eluting with 5% acetone/methylene chloride to give an additional 0.4 g. of product as a slightly colored solid. A small portion of the product is recrystallized from toluene to give (hexahydro-5-oxo-1,4-thiazepin-6-yl)carbamic acid, (1,1-dimethylethyl) ester as fine colorless needles; m.p. 199.5°-201°. TLC (10% acetone/methylene chloride) single spot at Rf =0.49.

Workup

  1. customto quench excess hydroxide
  2. customThe dioxane and water are evaporated
  3. customthe residual water is removed azeotropically with acetonitrile (twice)
  4. stirringstirred under argon at 25° for 3.5 days
  5. washwashed successively with water, saturated sodium bicarbonate, 5% potassium bisulfate, brine
  6. dry with materialdried (MgSO4)
  7. customevaporated
  8. temperatureupon cooling 1.1 g
  9. customof the product crystallizes as a colorless solid
  10. customThe mother liquor (1.9 g.) is chromatographed on silica (70 g.)
  11. washeluting with 5% acetone/methylene chloride
  12. customto give an additional 0.4 g
  13. customA small portion of the product is recrystallized from toluene

Sources & evidence

ORD record
ord-aa6954eb4f9b467098830f6da0001808
Source dataset
uspto-grants-1984_07
Patent number
US04460579

Reaction notes

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