Sodium Hydroxide → tert-butyl (1R,2R)-1-(6-bromopyridin-2-yl)-2-hydroxy-2-(3-methoxyphenyl)ethylcarbamate

HRID 2362333Notes

Reaction equation

HRID 2362333 reaction equation
[C:1](=[O:8])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])[NH2:2].[OH-].[Na+].Cl[O:12]C(C)(C)C.CC[C@@H]1[C@@H]2C[C@H]([C@@H](OC3C4C(=CC=CC=4)C(O[C@@H](C4C=CN=C5C=4C=C(OC)C=C5)[C@@H]4N5C[C@H](CC)[C@@H](CC5)C4)=NN=3)C3C=CN=C4C=3C=C(OC)C=C4)N(CC2)C1.[Br:75][C:76]1[CH:81]=[CH:80][CH:79]=[C:78](/[CH:82]=[CH:83]/[C:84]2[CH:89]=[CH:88][CH:87]=[C:86]([O:90][CH3:91])[CH:85]=2)[N:77]=1>C(O)CC.O>[Br:75][C:76]1[N:77]=[C:78]([C@@H:82]([NH:2][C:1](=[O:8])[O:3][C:4]([CH3:7])([CH3:6])[CH3:5])[C@H:83]([OH:12])[C:84]2[CH:89]=[CH:88][CH:87]=[C:86]([O:90][CH3:91])[CH:85]=2)[CH:79]=[CH:80][CH:81]=1

Participants

8

Reactant 5

HCID 14798Sodium HydroxideHCID 77922tert-Butyl carbamateHCID 521297Tert-Butyl hypochloriteHCID 112172021,4-Bis(dihydroquinidine)phthalazineHCID 86673403(E)-2-Bromo-6-(3-methoxystyryl)pyridine

Product 1

HCID 86673404tert-butyl (1R,2R)-1-(6-bromopyridin-2-yl)-2-hydroxy-2-(3-methoxyphenyl)ethylcarbamateYield 107%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 10311-PropanolSolvent3×

Conditions

Temperature
0 °C

Procedure

To tert-butyl carbamate (688 mg, 5.88 mmol) in propanol (10 mL) was added sodium hydroxide (231 mg, 5.78 mmol) in water (20 mL) followed by tert-butyl hypochlorite (0.652 mL, 5.78 mmol). The solution was cooled to 0° C. and (DHQD)2PHAL (89 mg, 0.114 mmol) was added in propanol (3 mL) followed by (E)-2-bromo-6-(3-methoxystyryl)pyridine (550 mg, 1.90 mmol) in propanol (10 mL). To this was added potassium osmate dihydrate (27.9 mg, 0.076 mmol) as a solid in one portion. The reaction was allowed to gradually warm to room temperature overnight. The reaction was placed in a cool bath (ca. 15° C.) and quenched by addition of sodiumthiosulfate (1.1 g) in water (8 mL). The reaction was stirred at room temperature for 30 min. The reaction was diluted with 1:1 diethylether/ethyl acetate, washed with water (2×), then brine, dried over magnesium sulfate, and concentrated. Column chromatography (20%-->50% EtOAc/Hex) gave 860 mg (107% yield) as a mixture of regioisomers. Mass spec.: 444.98 (MNa)+.

Workup

  1. temperatureto gradually warm to room temperature overnight
  2. customThe reaction was placed in a cool bath
  3. custom(ca. 15° C.) and quenched by addition of sodiumthiosulfate (1.1 g) in water (8 mL)
  4. additionThe reaction was diluted with 1:1 diethylether/ethyl acetate
  5. washwashed with water (2×)
  6. dry with materialbrine, dried over magnesium sulfate
  7. concentrationconcentrated
  8. customColumn chromatography (20%-->50% EtOAc/Hex) gave 860 mg (107% yield)
  9. additionas a mixture of regioisomers

Sources & evidence

ORD record
ord-acb4c38526284a628e1afa1012a1711e
Source dataset
uspto-grants-2014_04
Patent number
US08691821B2

Reaction notes

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