Sodium hydride → tert-butyl (2R,5R)-5-{[tert-butyl(dimethyl)silyl]oxy}-2-[2-(6-cyano-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)ethyl]piperidine-1-carboxylate

HRID 1644481Notes

Reaction equation

HRID 1644481 reaction equation
[Si:1]([O:8][C@H:9]1[CH2:14][N:13]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[C@@H:12]([CH2:22][CH2:23]O)[CH2:11][CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C(N(C(C)C)CC)(C)C.CS(Cl)(=O)=O.[O:39]=[C:40]1[NH:45][C:44]2[CH:46]=[C:47]([C:50]#[N:51])[CH:48]=[CH:49][C:43]=2[O:42][CH2:41]1.[H-].[Na+].S([O-])(=O)(=O)C>C(Cl)Cl.CN(C=O)C>[Si:1]([O:8][C@H:9]1[CH2:14][N:13]([C:15]([O:17][C:18]([CH3:21])([CH3:19])[CH3:20])=[O:16])[C@@H:12]([CH2:22][CH2:23][N:45]2[C:44]3[CH:46]=[C:47]([C:50]#[N:51])[CH:48]=[CH:49][C:43]=3[O:42][CH2:41][C:40]2=[O:39])[CH2:11][CH2:10]1)([C:4]([CH3:6])([CH3:5])[CH3:7])([CH3:3])[CH3:2]

Participants

9

Reactant 6

HCID 24758Sodium hydrideHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 85257MethanesulfonateHCID 106548133-Oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carbonitrile2×HCID 66774126tert-butyl(2R,5R)-5-{[tert-butyl(dimethyl)silyl]oxy}-2-(2-hydroxyethyl)piperidine-1-carboxylate2×

Product 1

HCID 66774834tert-butyl (2R,5R)-5-{[tert-butyl(dimethyl)silyl]oxy}-2-[2-(6-cyano-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)ethyl]piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of tert-butyl(2R,5R)-5-{[tert-butyl(dimethyl)silyl]oxy}-2-(2-hydroxyethyl)piperidine-1-carboxylate (Intermediate 187, 1.27 g) in methylene chloride (15 mL) at 0° C. were added diisopropylethylamine (1.2 mL) and methanesulfonyl chloride (0.50 mL). At the same time in a separate flask, to a solution of 3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carbonitrile (Intermediate 60) (0.66 g) in DMF (8 mL) at 0° C. was added 60% suspension in oil of NaH (0.25 g). After 30 minutes, the mesylate solution was diluted with methylene chloride, washed with NaHCO3 and brine, dried over sodium sulfate and concentrated. This residue was dissolved in DMF (5 mL) and added to the sodium salt of Intermediate 60. The reaction was stirred over the weekend, diluted with ethyl acetate, washed with NaHCO3 and brine, dried over sodium sulfate and concentrated to give the product.

Workup

  1. washwashed with NaHCO3 and brine
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated
  4. dissolutionThis residue was dissolved in DMF (5 mL)
  5. additionadded to the sodium salt of Intermediate 60
  6. additiondiluted with ethyl acetate
  7. washwashed with NaHCO3 and brine
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated
  10. customto give the product

Sources & evidence

ORD record
ord-a6200cc78f294e6d8c667a10483ac328
Source dataset
uspto-grants-2012_02
Patent number
US08124602B2

Reaction notes

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