Hydrochloric Acid → Ethyl (1S,3R,4R)-3-[[(1,1-dimethylethoxy)carbonyl]amino]-4-[(methylsulfonyl)oxy]cyclohexanecarboxylate

HRID 546457Notes

Reaction equation

HRID 546457 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]1[C@H:14]([OH:15])[CH2:13][CH2:12][C@H:11]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[CH3:28][S:29](Cl)(=[O:31])=[O:30].Cl>ClCCl>[C:1]([O:5][C:6]([NH:8][C@H:9]1[C@H:14]([O:15][S:29]([CH3:28])(=[O:31])=[O:30])[CH2:13][CH2:12][C@H:11]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 59676815(1S,3R,4R)-3-(Boc-aMino)-4-hydroxy-cyclohexanecarboxylic acid ethyl ester

Product 1

HCID 86593060Ethyl (1S,3R,4R)-3-[[(1,1-dimethylethoxy)carbonyl]amino]-4-[(methylsulfonyl)oxy]cyclohexanecarboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Ethyl (1S,3R,4R)-3-(tert-butoxycarbonylamino)-4-hydroxycyclohexane-1-carboxylate (53.5 g) and triethylamine (130 ml) were dissolved in dichloromethane (500 ml), and methanesulfonyl chloride (42 ml) was added dropwise while cooling the solution to −10° C. to −15° C. After stirring for 20 minutes at the same temperature, the mixture was heated to room temperature over 30 minutes and further stirred for 2 hours. The reaction mixture was cooled to 0° C., 0.5N hydrochloric acid (800 ml) was added dropwise, and the mixture was extracted with dichloromethane. The resultant organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate and saturated saline and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain crude ethyl (1S,3R,4R)-3-(tert-butoxycarbonylamino)-4-(methane-sulfonyloxy)cyclohexane-1-carboxylate.

Workup

  1. temperaturewhile cooling the solution to −10° C. to −15° C
  2. stirringfurther stirred for 2 hours
  3. temperatureThe reaction mixture was cooled to 0° C.
  4. extractionthe mixture was extracted with dichloromethane
  5. washThe resultant organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate and saturated saline
  6. dry with materialdried over anhydrous magnesium sulfate
  7. distillationThe solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-a811e84407454873be8a39fe6351da7e
Source dataset
uspto-grants-2011_05
Patent number
US07935824B2

Reaction notes

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