Carbonate Ion → Methyl 4-(4-[[(4-[[(tert-butoxy)carbonyl]amino]cyclohexyl)sulfanyl]methyl]-5-methyl-1,3-oxazol-2-yl)benzoate

HRID 1526860Notes

Reaction equation

HRID 1526860 reaction equation
[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:16]=[CH:15][C:10]([C:11]([O:13][CH3:14])=[O:12])=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:17][SH:18].C(=O)([O-])[O-].CS(O[CH:28]1[CH2:33][CH2:32][CH:31]([NH:34][C:35](=[O:41])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38])[CH2:30][CH2:29]1)(=O)=O>CN(C)C=O>[C:37]([O:36][C:35]([NH:34][CH:31]1[CH2:32][CH2:33][CH:28]([S:18][CH2:17][C:3]2[N:4]=[C:5]([C:7]3[CH:8]=[CH:9][C:10]([C:11]([O:13][CH3:14])=[O:12])=[CH:15][CH:16]=3)[O:6][C:2]=2[CH3:1])[CH2:29][CH2:30]1)=[O:41])([CH3:40])([CH3:38])[CH3:39]

Participants

5

Reactant 3

HCID 19660Carbonate IonHCID 21882613trans-4-(Boc-amino)cyclohexyl methanesulfonateHCID 86709134Methyl 4-[5-methyl-4-(sulfanylmethyl)-1,3-oxazol-2-yl]benzoate

Product 1

HCID 68278174Methyl 4-(4-[[(4-[[(tert-butoxy)carbonyl]amino]cyclohexyl)sulfanyl]methyl]-5-methyl-1,3-oxazol-2-yl)benzoateYield 15%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

Into a 100-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed A mixture of methyl 4-[5-methyl-4-(sulfanylmethyl)-1,3-oxazol-2-yl]benzoate (3 g, 11.39 mmol, 1.00 equiv), cescium carbonate (5.13 g, 15.70 mmol, 1.39 equiv) and tert-butyl N-[4-(methanesulfonyloxy)cyclohexyl]carbamate (3.22 g, 10.98 mmol, 1.20 equiv) in N,N-dimethylformamide (30 mL) was stirred at 50° C. for 3 h. The reaction was quenched by the addition of 50 mL of water and the resulting solution was extracted with 3×60 mL of ethyl acetate. The organic combined layers was washed with 2×200 mL of brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified on\ a silica gel column eluted with ethyl acetate/petroleum ether (1:15-1:5). The collected fractions were combined and concentrated under vacuum to give 760 mg (14%) of methyl 4-(4-[[(4-[[(tert-butoxy)carbonyl]amino]cyclohexyl)sulfanyl]methyl]-5-methyl-1,3-oxazol-2-yl)benzoate as a yellow solid. LC-MS: (ES, m/z): 461 [M+H]+, 405, 361, 271, 230, 115.

Workup

  1. customInto a 100-mL 3-necked round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. customThe reaction was quenched by the addition of 50 mL of water
  4. extractionthe resulting solution was extracted with 3×60 mL of ethyl acetate
  5. washThe organic combined layers was washed with 2×200 mL of brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under vacuum
  8. customThe residue was purified on\ a silica gel column
  9. washeluted with ethyl acetate/petroleum ether (1:15-1:5)
  10. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-5e5e1b6e354e4f4cbee19f14c05cf79d
Source dataset
uspto-grants-2015_07
Patent number
US09085570B2

Reaction notes

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