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

HRID 1747117Notes

Reaction equation

HRID 1747117 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].[C:28]([Si:32]([O:35][CH2:36][CH2:37]I)([CH3:34])[CH3:33])([CH3:31])([CH3:30])[CH3:29].Cl>C1COCC1.O>[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:28]([CH3:31])([CH3:30])[CH3:29])([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

7

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 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To a solution of LiHMDS in THF (72.9 mL of a 1 M solution, 72.9 mmol, 2.2 eq) at −78° C. under Ar was added a solution of (1R,4S)-methyl 4-((t-butoxycarbonyl)amino)cyclopent-2-enecarboxylate (prepared according to the procedure of US 20050101628 A1 (see page 31, column 1, Procedure B, step B)), 8.00 g, 33.2 mmol, 1 eq) in THF (40 mL) dropwise over 1 hr. After stirring for 30 min, a solution of t-butyl(2-iodoethoxy)dimethylsilane (13.29 g, 46.4 mmol, 1.4 eq) in THF (20 mL) was added. The solution was kept at −78° C. for 15 min, then gradually warmed to 0° C. over 2 hrs, and kept at 0° C. for 1 hr. 1 N HCl and water were added, the solution extracted with DCM, the organics combined, dried over MgSO4, and concentrated. Purification by chromatography (400 g column) eluting with 5 to 20% EtOAc/heptane afforded the title compound of Step A. 1H NMR (CHLOROFORM-d) δ: 5.76-5.85 (m, 2H), 4.90 (d, J=9.0 Hz, 1H), 4.72-4.82 (m, 1H), 3.69 (s, 3H), 3.57-3.64 (m, 2H), 2.24 (dd, J=13.9, 8.0 Hz, 1H), 2.14 (dd, J=14.1, 3.5 Hz, 2H), 1.71-1.82 (m, 1H), 1.40-1.50 (m, 9H), 0.84-0.90 (m, 9H), 0.03 (s, 6H). ESI-MS (m/z): Calculated for C20H37NO5Si: 422.2 (M+23). found: 422.2.

Workup

  1. customprepared
  2. customdropwise over 1 hr
  3. waitThe solution was kept at −78° C. for 15 min
  4. waitkept at 0° C. for 1 hr
  5. extractionthe solution extracted with DCM
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customPurification by chromatography (400 g column)
  9. washeluting with 5 to 20% EtOAc/heptane

Sources & evidence

ORD record
ord-ba0ea436146e44138721b69d99702da0
Source dataset
uspto-grants-2015_10
Patent number
US09150532B2

Reaction notes

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