Hydrochloric Acid → 4-{[4-({[Tert-butyl(dimethyl)silyl]oxy}methyl)-2-chloro-1,3-thiazol-5-yl]carbonyl}morpholine

HRID 1948357Notes

Reaction equation

C[Al](C)C.[NH:5]1[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1.[Si:11]([O:18][CH2:19][C:20]1[N:21]=[C:22]([Cl:30])[S:23][C:24]=1[C:25](OCC)=[O:26])([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12].Cl>C(Cl)Cl>[Si:11]([O:18][CH2:19][C:20]1[N:21]=[C:22]([Cl:30])[S:23][C:24]=1[C:25]([N:5]1[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1)=[O:26])([C:14]([CH3:17])([CH3:15])[CH3:16])([CH3:13])[CH3:12]

Participants

Conditions

Temperature: 80 °C

Procedure

A solution of 2N Me3Al in hexanes (0.91 ml, 1.82 mmol) was added slowly to a solution of 0.16 ml (1.8 mmol) of morpholine in 4 ml CH2Cl2. After stirring for 15 min, a solution of 0.5 g (1.5 mmol) of ethyl 4-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-chloro-1,3-thiazole-5-carboxylate (Intermediate 218) in 4 ml CH2Cl2 was added. The solution was heated at 80° C. in a microwave reactor for 1 hour before pouring into dilute aqueous HCl. The mixture was extracted 3 times with CH2Cl2, which was washed with brine, dried (MgSO4) and concentrated. The residue was purified by silica gel chromatography (100% CH2Cl2 followed by gradient elution to 30% EtOAc in CH2Cl2 to give 315 mg of product. MS (ES) (MH+): 377 for C15H25ClN2O3SSi; NMR (d6-DMSO): 0.1 (s, 6H), 0.9 (s, 9H), 3.6 (m, 4H), 3.7 (m, 4H), 4.1 (q, 2H), 4.75 (s, 2H).

Workup

extractionThe mixture was extracted 3 times with CH2Cl2, which
washwas washed with brine
dry with materialdried (MgSO4)
concentrationconcentrated
customThe residue was purified by silica gel chromatography (100% CH2Cl2
washfollowed by gradient elution to 30% EtOAc in CH2Cl2

Sources & evidence

ORD record: ord-ce6c97b4ec884225886c5a4056ae9d3d
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08399489B2

Reaction notes

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