Potassium bisulfate → (4R)-4-{[6-(Benzyloxy)pyridin-2-yl]oxy}-1-(tert-butoxycarbonyl)-L-proline

HRID 1255521

反応式

HRID 1255521 の反応式
[CH3:1][C:2]([O:5][C:6]([N:8]1[C@H:12]([C:13]([OH:15])=[O:14])[CH2:11][CH:10]([OH:16])[CH2:9]1)=[O:7])([CH3:4])[CH3:3].[CH2:17]([O:24][C:25]1[CH:30]=[CH:29][CH:28]=[C:27](F)[N:26]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.CC(C)([O-])C.[K+].S(=O)(=O)(O)[O-].[K+]>CS(C)=O>[CH2:17]([O:24][C:25]1[N:26]=[C:27]([O:16][C@H:10]2[CH2:9][N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[C@H:12]([C:13]([OH:15])=[O:14])[CH2:11]2)[CH:28]=[CH:29][CH:30]=1)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

参加物

6

反応物 4

HCID 516920Potassium bisulfateHCID 111389801-(1,1-Dimethylethyl) (2S)-4-hydroxy-1,2-pyrrolidinedicarboxylateHCID 23665647Potassium tert-butoxideHCID 577538712-(Benzyloxy)-6-fluoropyridine

生成物 1

HCID 58158006(4R)-4-{[6-(Benzyloxy)pyridin-2-yl]oxy}-1-(tert-butoxycarbonyl)-L-proline収率 100%

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒2 回

実験手順

A 500 mL 3-neck round bottom flask under nitrogen was charged with Boc-L-4-hydroxyproline (Chem Impex) (2.00 g, 8.65 mmol) and DMSO (80 ml). Attached an addition funnel containing a solution of the product of Step 1 (1.758 g, 8.65 mmol) in DMSO (10 ml). Cooled reaction in an ice bath to +18° C. Added potassium-t-butoxide (2.91 g, 25.9 mmol) slowly keeping the internal temperature<20° C. Stirred 45 minutes at room temperature. Cooled to 15° C. Added contents of addition funnel dropwise. Warmed to room temperature. Stirred 1.5 hours. Poured into 2.5% potassium bisulfate. Extracted three times with ethyl acetate, washed combined organic portions with water then brine, dried with anhydrous magnesium sulfate, filtered and rotary evaporated filtrate to give the title compound as a white foam. (3.58 g, 8.65 mmol, 100% yield). LCMS (ES+) m/z 415.3 (M+H)+.

後処理

  1. temperatureCooled
  2. customreaction in an ice bath to +18° C
  3. customthe internal temperature<20° C
  4. temperatureCooled to 15° C
  5. additionAdded contents of addition funnel dropwise
  6. temperatureWarmed to room temperature
  7. stirringStirred 1.5 hours
  8. extractionExtracted three times with ethyl acetate
  9. washwashed
  10. dry with materialbrine, dried with anhydrous magnesium sulfate
  11. filtrationfiltered

出典と根拠

ORDレコード
ord-06acae8a1b5a4158b3f7d4b686e66eae
出典データセット
uspto-grants-2013_06
特許番号
US08461107B2

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