Water → tert-butyl N-(3-hydroxy-3-methylcyclobutyl)carbamate

HRID 577723ノート

反応式

HRID 577723 の反応式
[C:1]([O:5][C:6](=[O:14])[NH:7][CH:8]1[CH2:13][C:10]2([O:12][CH2:11]2)[CH2:9]1)([CH3:4])([CH3:3])[CH3:2].C([BH-](CC)CC)C.[Li+].O.C(=O)([O-])[O-].[K+].[K+]>C1COCC1>[C:1]([O:5][C:6](=[O:14])[NH:7][CH:8]1[CH2:13][C:10]([OH:12])([CH3:11])[CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

参加物

6

反応物 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 23664628LithiumtriethylborohydrideHCID 58520785tert-butyl N-(1-oxaspiro(2.3)hexan-5-yl)carbamate

生成物 1

HCID 72207356tert-butyl N-(3-hydroxy-3-methylcyclobutyl)carbamate収率 80%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

(1-Oxa-spiro[2.3]hex-5-yl)-carbamic acid tert-butyl ester (˜1:1 cis/trans mixture, 3.93 g, 19.7 mmol) was dissolved in anhydrous THF (100 mL) and cooled to 0° C. in an ice/water bath. To this was added a 1.0 M solution of lithium triethylborohydride in THF (25 mL) via dropping addition funnel, over 10 min, then the mixture stirred at 0° C. for 3.5 hours. While still cooled to 0° C., 30 mL deionized water was added dropwise over 5 minutes to quench the reaction. After warming to rt, solid potassium carbonate was added to saturate the aqueous phase, allowing the layers to be separated. The aqueous layer was further extracted with ethyl acetate (2×30 mL). The combined organic layers (THF and EtOAc) were dried over magnesium sulfate, filtered, concentrated, and purified by silica gel chromatography (eluting with 40-80% ethyl acetate in heptanes), affording the title compound (3.16 g, 80%) as a white solid. NMR shows a 55:45 ratio of N,O-cis/trans isomers. 1H NMR (400 MHz, chloroform-d) δ ppm [1.37 (s) and 1.41 (s), 3H together] 1.44 (s, 9H) 1.66 (br. s., 1H) 1.89-2.03 (m, 2H) 2.42-2.54 (m, 2H)

後処理

  1. additionaddition funnel
  2. temperatureWhile still cooled to 0° C.
  3. additionwas added dropwise over 5 minutes
  4. customto quench
  5. customthe reaction
  6. temperatureAfter warming to rt
  7. concentrationto saturate the aqueous phase
  8. customto be separated
  9. extractionThe aqueous layer was further extracted with ethyl acetate (2×30 mL)
  10. dry with materialThe combined organic layers (THF and EtOAc) were dried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. custompurified by silica gel chromatography (eluting with 40-80% ethyl acetate in heptanes)

出典と根拠

ORDレコード
ord-9662147676074295a049cf8e435548dd
出典データセット
uspto-grants-2015_05
特許番号
US09040547B2

反応ノート

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