Lithium tri-s-butylborohydride → Bis[(2-fluorophenyl)methyl](1S,2S,4S,5R,6R)-2-(tert-butoxycarbonylamino)-4-hydroxy-bicyclo[3.1.0]hexane-2,6-dicarboxylate

HRID 1879578ノート

反応式

HRID 1879578 の反応式
CCC(C)[BH-](C(C)CC)C(C)CC.[Li+].[F:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[CH2:22][O:23][C:24]([C@:26]1([NH:44][C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[CH2:31][C:30](=[O:32])[C@@H:29]2[C@H:27]1[C@H:28]2[C:33]([O:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=1[F:43])=[O:34])=[O:25].FC1C=CC=CC=1COC([C@]1(NC(OC(C)(C)C)=O)C[C@@H](O)[C@@H]2[C@H]1[C@H]2C(OCC1C=CC=CC=1F)=O)=O>O1CCCC1>[F:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[CH2:22][O:23][C:24]([C@:26]1([NH:44][C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[CH2:31][C@H:30]([OH:32])[C@@H:29]2[C@H:27]1[C@H:28]2[C:33]([O:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=1[F:43])=[O:34])=[O:25]

参加物

5

反応物 3

HCID 3611392Lithium tri-s-butylborohydrideHCID 58319579HCID 58319579、化合物2 回HCID 67238319bis[(2-fluorophenyl)methyl](1S,2S,4R,5R,6R)-2-(tert-butoxycarbonylamino)-4-hydroxy-bicyclo[3.1.0]hexane-2,6-dicarboxylate

生成物 1

HCID 58319587Bis[(2-fluorophenyl)methyl](1S,2S,4S,5R,6R)-2-(tert-butoxycarbonylamino)-4-hydroxy-bicyclo[3.1.0]hexane-2,6-dicarboxylate

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

Add 1M L-selectride solution in THF (6.78 mL, 6.78 mmol) dropwise to a stirred solution of bis[(2-fluorophenyl)methyl](1S,2S,5R,6R)-2-(tert-butoxycarbonylamino)-4-oxo-bicyclo[3.1.0]hexane-2,6-dicarboxylate (2.33 g, 4.52 mmol) in tetrahydrofuran (20.3 mL) at −78° C. Stir the resulting orange mixture under nitrogen for 1 hour 45 minutes. Quench with a saturated solution of sodium hydrogen carbonate at −78° C. Dilute with water and ethyl acetate. Separate the layers and wash the organic phase with brine and water. Dry over sodium sulfate, filter and concentrate to dryness to give the crude material as pale yellow oil contaminated with approximately 6% of the minor isomer bis[(2-fluorophenyl)methyl](1S,2S,4R,5R,6R)-2-(tert-butoxycarbonylamino)-4-hydroxy-bicyclo[3.1.0]hexane-2,6-dicarboxylate as detected by MS. Combine the crude material with a second batch similarly prepared from bis[(2-fluorophenyl)methyl](1S,2S,5R,6R)-2-(tert-butoxycarbonylamino)-4-oxo-bicyclo[3.1.0]hexane-2,6-dicarboxylate (0.23 g, 0.44 mmol). Purify the combined material by flash chromatography eluting with ethyl acetate:hexane (20:80 to 50:50) to give the title product as a single isomer (2.49 g, 4.81 mmol). MS (m/z): 540 (M+23).

後処理

  1. customQuench with a saturated solution of sodium hydrogen carbonate at −78° C
  2. additionDilute with water and ethyl acetate
  3. customSeparate the layers
  4. washwash the organic phase with brine and water
  5. dry with materialDry over sodium sulfate
  6. filtrationfilter
  7. concentrationconcentrate to dryness
  8. customto give the crude material as pale yellow oil
  9. customPurify the combined material by flash chromatography
  10. washeluting with ethyl acetate:hexane (20:80 to 50:50)

出典と根拠

ORDレコード
ord-7806cc7d36314bb28db1ecc92a07ba65
出典データセット
uspto-grants-2012_11
特許番号
US08318184B2

反応ノート

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