Hydrochloric Acid → (1S,4S)-methyl 4-(tert-butoxycarbonylamino)-1-(2-(tert-butyldimethylsilyloxy)ethyl)cyclopent-2-enecarboxylate

HRID 1747142Notes

Reaction equation

HRID 1747142 reaction equation
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[C:11]([O:15][C:16]([NH:18][C@H:19]1[CH2:23][C@@H:22]([C:24]([O:26][CH3:27])=[O:25])[CH:21]=[CH:20]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].[CH3:28][C:29]([Si:32]([O:35][CH2:36][CH2:37]I)([CH3:34])[CH3:33])([CH3:31])[CH3:30].Cl>C1COCC1>[C:11]([O:15][C:16]([NH:18][C@H:19]1[CH2:23][C@@:22]([CH2:37][CH2:36][O:35][Si:32]([C:29]([CH3:31])([CH3:30])[CH3:28])([CH3:34])[CH3:33])([C:24]([O:26][CH3:27])=[O:25])[CH:21]=[CH:20]1)=[O:17])([CH3:14])([CH3:13])[CH3:12]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 2733832Lithium HexamethyldisilazideHCID 10610130(1R,4S)-methyl 4-(tert-butoxycarbonylamino)cyclopent-2-enecarboxylateHCID 11129873tert-Butyl(2-iodoethoxy)dimethylsilane

Product 1

HCID 86708127(1S,4S)-methyl 4-(tert-butoxycarbonylamino)-1-(2-(tert-butyldimethylsilyloxy)ethyl)cyclopent-2-enecarboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-68 °C

Procedure

To a −70° C. solution of LiHMDS in THF (1M, 6.97 L, 6.97 mol) was added a solution of the product of Step B (763.5 g, 3.16 mol) in THF (800 mL) over a 2 h period while keeping the temperature at or below −68° C. The resulting solution was stirred for 45 min at −68° C. A solution of the product of Step C (1.267 kg, 4.426 mol) in THF (800 mL) was added over 1 h 50 min period while maintaining a temperature of ˜−66° C. The reaction was stirred at ˜-66° C. for 45 min. The reaction was warmed to −15° C. and worked up by addition to mixture of aqueous HCl and ice. The mixture was extracted with toluene, the organic layer was washed with water, brine and dried over MgSO4. The organic layer was concentrated and purified on silica gel using a mixture of EtOAc in heptanes to provide the product of Step D as a clear oil. 1H NMR (400 MHz, CHLOROFORM-d) d=5.69-5.86 (m, 2H), 4.79-4.93 (m, 1H), 4.68-4.80 (m, 1H), 3.67 (s, 3H), 3.53-3.62 (m, 2H), 2.16-2.30 (m, 1H), 2.04-2.16 (m, 2H), 1.70-1.81 (m, 1H), 1.41 (s, 9H), 0.78-0.91 (m, 13H), 0.00 (s, 6H).

Workup

  1. custombelow −68° C
  2. temperaturewhile maintaining a temperature of ˜−66° C
  3. stirringThe reaction was stirred at ˜-66° C. for 45 min
  4. temperatureThe reaction was warmed to −15° C.
  5. extractionThe mixture was extracted with toluene
  6. washthe organic layer was washed with water, brine
  7. dry with materialdried over MgSO4
  8. concentrationThe organic layer was concentrated
  9. custompurified on silica gel using
  10. additiona mixture of EtOAc in heptanes

Sources & evidence

ORD record
ord-ffd8eef9413c4e0f99f1683a2c9e791d
Source dataset
uspto-grants-2015_10
Patent number
US09150532B2

Reaction notes

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