Potassium Carbonate → (2R,3S)-2-(3-chloro-7-cyanobenzo[b]thiophen-4-ylamino)-3-hydroxybutanoic acid

HRID 470910Notes

Reaction equation

C([O-])([O-])=O.[K+].[K+].[Cl:7][C:8]1[C:9]2[C:16](F)=[CH:15][CH:14]=[C:13]([C:18]#[N:19])[C:10]=2[S:11][CH:12]=1.[NH2:20][C@@H:21]([C:25]([OH:27])=[O:26])[C@H:22]([CH3:24])[OH:23]>CS(C)=O>[Cl:7][C:8]1[C:9]2[C:16]([NH:20][C@H:21]([C@@H:22]([OH:23])[CH3:24])[C:25]([OH:27])=[O:26])=[CH:15][CH:14]=[C:13]([C:18]#[N:19])[C:10]=2[S:11][CH:12]=1

Participants

Conditions

Temperature: 80 °C

Procedure

K2CO3 (850 mg, 6.15 mmol) was added to a mixture of 3-chloro-4-fluorobenzo[b]thiophene-7-carbonitrile (0.52 g, 2.46 mmol) and D-threonine (322 mg, 2.70 mmol) in DMSO (10 mL) at room temperature. The mixture was heated to 80° C. and stirred for 16 h. After cooling to room temperature, the reaction mixture was poured into ice-water (100 mL) and extracted with 10% EtOAc in hexanes (2×50 mL). The aqueous phase was acidified to pH=2˜3 with 2N HCl and extracted with EtOAc (2×100 mL). The EtOAc extracts were washed with water, brine and dried over Na2SO4. Removal of the solvent gave the crude (2R,3S)-2-(3-chloro-7-cyanobenzo[b]thiophen-4-ylamino)-3-hydroxybutanoic acid (0.73 g, 96%). 1H NMR (400 MHz, Acetone-d6, δ in ppm) 7.67 (s, 1H), 7.65 (d, J=8.5 Hz, 1H), 7.45 (d, J=8.4 Hz, 1H), 6.64 (d, J=8.5 Hz, 1H), 4.57 (m, 1H), 4.35 (dd, J=2.4, 8.4 Hz, 1H), 1.37 (d, J=6.5 Hz, 3H).

Workup

temperatureAfter cooling to room temperature
extractionextracted with 10% EtOAc in hexanes (2×50 mL)
extractionextracted with EtOAc (2×100 mL)
washThe EtOAc extracts were washed with water, brine
dry with materialdried over Na2SO4
customRemoval of the solvent

Sources & evidence

ORD record: ord-a5d76725a0e44ae792d3fd46e0036898
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08629167B2

Reaction notes

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