Dimethylformamide → Tert-butyl[4-(3,5-difluoro-benzyl)-5-oxoperhydro-1,4-thiazepin-6-yl]carbamate

HRID 1986539Notes

Reaction equation

HRID 1986539 reaction equation
[H-].[Na+].CN(C=O)C.[O:8]=[C:9]1[CH:15]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:14][S:13][CH2:12][CH2:11][NH:10]1.[F:24][C:25]1[CH:26]=[C:27]([CH:30]=[C:31]([F:33])[CH:32]=1)[CH2:28]Br>O.CCOC(C)=O>[F:24][C:25]1[CH:26]=[C:27]([CH:30]=[C:31]([F:33])[CH:32]=1)[CH2:28][N:10]1[C:9](=[O:8])[CH:15]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:20])([CH3:22])[CH3:21])[CH2:14][S:13][CH2:12][CH2:11]1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 5188963,5-Difluorobenzyl bromideHCID 15591256(Hexahydro-5-oxo-1,4-thiazepin-6-yl)carbamic acid, (1,1-dimethylethyl) ester

Product 1

HCID 57722274Tert-butyl[4-(3,5-difluoro-benzyl)-5-oxoperhydro-1,4-thiazepin-6-yl]carbamateYield 79%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

121 mg of sodium hydride as a 60% suspension in oil (3.05 mmol) are introduced at room temperature into a 50 ml round-bottomed flask, with stirring and under an argon atmosphere, containing 20 ml of DMF and 500 mg of 26 (2.03 mmol). The medium is stirred for 1 hour and 454 mg (2.03 mmol) of 3,5-difluorobenzyl bromide are then added. The medium is stirred for 3 hours, 50 ml of EtOAc and 50 ml of water are added to the reaction medium and, after separation of the phases by settling, the organic phase is washed with 50 ml of water. The organic phase is dried, filtered and then evaporated to dryness. 1.5 g of crude product are recovered, which product is chromatographed on a silica cartridge (20 g, eluent: 80/20 heptane/EtOAc). 600 mg of product 33 are recovered (yield=79%).

Workup

  1. stirringThe medium is stirred for 1 hour
  2. stirringThe medium is stirred for 3 hours
  3. customafter separation of the phases
  4. washthe organic phase is washed with 50 ml of water
  5. customThe organic phase is dried
  6. filtrationfiltered
  7. customevaporated to dryness
  8. custom1.5 g of crude product are recovered
  9. customwhich product is chromatographed on a silica cartridge (20 g, eluent: 80/20 heptane/EtOAc)
  10. custom600 mg of product 33 are recovered (yield=79%)

Sources & evidence

ORD record
ord-bc936704ed794c1d9f6b66758f70e013
Source dataset
uspto-grants-2009_06
Patent number
US07550453B2

Reaction notes

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