Dimethylformamide → HCID 86728127, compound

HRID 627660Notes

Reaction equation

HRID 627660 reaction equation
[C:1]([O:5][C:6](=[O:36])[N:7]([C:15]1[C:16]([CH3:35])([CH3:34])[S:17](=[O:33])(=[O:32])[CH2:18][C@:19]([C:22]2[CH:27]=[C:26]([N+:28]([O-:30])=[O:29])[CH:25]=[CH:24][C:23]=2F)([CH3:21])[N:20]=1)[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])([CH3:4])([CH3:3])[CH3:2].CN(C=[O:41])C.C(=O)([O-])[O-].[Cs+].[Cs+].CS(CCO)(=O)=O>CCOC(C)=O.[Cl-].[NH4+]>[C:1]([O:5][C:6](=[O:36])[N:7]([C:15]1[C:16]([CH3:35])([CH3:34])[S:17](=[O:33])(=[O:32])[CH2:18][C@:19]([C:22]2[CH:27]=[C:26]([N+:28]([O-:30])=[O:29])[CH:25]=[CH:24][C:23]=2[OH:41])([CH3:21])[N:20]=1)[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonate2×HCID 848342-(Methylsulfonyl)ethanolHCID 86728128HCID 86728128, compound

Product 1

HCID 86728127HCID 86728127, compoundYield 94.4%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 25517Ammonium ChlorideSolvent

Procedure

To a solution of (R)-tert-butyl-N-(5-(2-fluoro-5-nitrophenyl)-2,2,5-trimethyl-1,1-dioxido-5,6-dihydro-2H-1,4-thiazin-3-yl)-N-tert-butoxycarbonyl-carbamate (1.00 g, 1.888 mmol) (prepared according to the procedure detailed in Intermediate 32, Step 1) in DMF (8 ml) 2-(methylsulphonyl)ethanol (0.49 g, 3.95 mmol) and cesium carbonate (1.28 g, 3.93 mmol) were added and the mixture was stirred overnight at rt. Additional Cs2CO3 (610 mg, 1 eq) and 2-(methylsulphonyl)ethanol (250 mg, 1 eq) were added and stirring continued for additional 2 hrs. The mixture was diluted with EtOAc and saturated ammonium chloride. Organic layer was separated and washed twice with water, then with brine and concentrated. The residue was purified by FC on 40 g RediSep Gold column using 5-100% EtOAc in heptane to afford (R)-tert-butyl-N-(5-(2-hydroxy-5-nitrophenyl)-2,2,5-trimethyl-1,1-dioxido-5,6-dihydro-2H-1,4-thiazin-3-yl)-N-tert-butoxylcarbonyl-carbamate (940 mg, 1.782 mmol, 94% yield). LC/MS (ESI+) m/z=550 (M+Na)

Workup

  1. stirringstirring
  2. waitcontinued for additional 2 hrs
  3. customOrganic layer was separated
  4. washwashed twice with water
  5. concentrationwith brine and concentrated
  6. customThe residue was purified by FC on 40 g RediSep Gold column

Sources & evidence

ORD record
ord-d6902cc8ef9a48c1955fb9e52921dce4
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

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