Hydrochloric Acid → 3-Hydroxy-2-methoxy-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-yl}-propionic Acid Methyl Ester

HRID 855956Notes

Reaction equation

HRID 855956 reaction equation
[CH3:1][O:2][C:3](=[O:7])[CH2:4][O:5][CH3:6].[Li+].CC([N-]C(C)C)C.[CH3:16][C:17]1[O:21][C:20]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[N:19][C:18]=1[CH2:28][CH2:29][O:30][C:31]1[C:39]2[CH:38]=[CH:37][S:36][C:35]=2[C:34]([CH:40]=[O:41])=[CH:33][CH:32]=1.Cl>C1COCC1.ClCCl.ClCCl.CCOC(C)=O>[CH3:1][O:2][C:3](=[O:7])[CH:4]([O:5][CH3:6])[CH:40]([OH:41])[C:34]1[C:35]2[S:36][CH:37]=[CH:38][C:39]=2[C:31]([O:30][CH2:29][CH2:28][C:18]2[N:19]=[C:20]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[O:21][C:17]=2[CH3:16])=[CH:32][CH:33]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 80507Methyl methoxyacetateHCID 2724682Lithium diisopropylamideHCID 111759364-[2-(5-Methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-1-benzothiophene-7-carbaldehyde

Product 1

HCID 589954383-Hydroxy-2-methoxy-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-yl}-propionic Acid Methyl EsterYield 92%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 21226138Dichloromethane ethylacetateSolvent

Procedure

To a solution of 3.17 ml methoxyacetic acid methyl ester (31.4 mmol) in 30 ml of THF, 17 ml of LDA (2M in THF/heptane/ethylbenzene, 34.2 mmol) were added dropwise within 15 min at −78° C. After stirring for additional 15 min, a solution of 5.00 g of 4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-carbaldehyde (13.7 mmol) in 70 ml of dichloromethane was added dropwise within 20 min. The dark brown reaction solution was stirred for additional 60 min, then warm up to room temperature within 150 min, cooled to 0° C. again and treated with 50 ml of ice water and 6 ml of conc. hydrochloric acid (pH 3). The organic layer was separated, washed with 25 ml water, dried over sodium sulfate and evaporated to dryness to yield 8.81 g of crude product as a brown oil. Flash chromatography (SiO2, dichloromethane/AcOEt=9/1) yielded 5.89 g (91%) of the title compound as a syn/anti mixture of 1:4 with a purity of 98.3% (GC area; method: column: DB-1 (15 m*0.32 mm); injector: 270° C.; detector: 320° C.; oven 150-310° C. (4° C./); carrier gas: H2 (60 KPa); samples silylated with BSTFA/pyridine. Retention times: starting material (aldehyde 1), 23.8 min; syn-alcohol 6, 28.1 min; anti-alcohol 6, 28.5 min) as a yellowish crystalline solid.

Workup

  1. stirringThe dark brown reaction solution was stirred for additional 60 min
  2. temperaturecooled to 0° C. again
  3. customThe organic layer was separated
  4. washwashed with 25 ml water
  5. dry with materialdried over sodium sulfate
  6. customevaporated to dryness
  7. customto yield 8.81 g of crude product as a brown oil

Sources & evidence

ORD record
ord-fff1bb568e524b1cbbe08d4acedc7d57
Source dataset
uspto-grants-2007_08
Patent number
US07262303B2

Reaction notes

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