Tetrahydrofuran → 1,1-Dimethylethyl 6-cyano-3,5-dihydroxyhexanoate

HRID 1062826ノート

反応式

HRID 1062826 の反応式
[C:1]([CH2:3][CH:4]([OH:16])[CH2:5][C:6](=[O:15])[CH2:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])#[N:2].C(B(CC)OC)C.O1CCCC1.[BH4-].[Na+]>CO.COCCOCCOCCOC>[C:1]([CH2:3][CH:4]([OH:16])[CH2:5][CH:6]([OH:15])[CH2:7][C:8]([O:10][C:11]([CH3:12])([CH3:14])[CH3:13])=[O:9])#[N:2]

参加物

7

反応物 4

HCID 8028TetrahydrofuranHCID 522516DiethylmethoxyboraneHCID 4311764Sodium borohydrideHCID 11637184Tert-butyl 6-cyano-5-hydroxy-3-oxohexanoate

生成物 1

HCID 222829971,1-Dimethylethyl 6-cyano-3,5-dihydroxyhexanoate

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 8189Triglyme溶媒

実験手順

Crude 5R 1,1-dimethylethyl 6-cyano-5-hydroxy-3-oxohexanoate (about 150 mmoles) is dissolved by adding 22 mL diethylmethoxyborane and 200 mL tetrahydrofuran. The solution is stirred for about 2 hours at room temperature, then cooled to −70° C. to −75° C., and further diluted with 25 mL methanol. Sodium borohydride (6 g) as a solution in triglyme (75 mL) is added slowly at between −65° C. to −75° C. After the addition, the reaction mixture is warmed to 15° C. to 25° C., quenched by the addition of acetic acid and concentrated by vacuum distillation—keeping this distillate. The residue is diluted with methanol and concentrated by vacuum distillation—keeping this distillate and all subsequent ones separate from the first one. The residue is dissolved in a mixture of water and ethyl acetate, the layers separated, and the organic layer is concentrated by vacuum distillation. The residue is dissolved in methanol and acetic acid and concentrated by vacuum distillation. The residue is dissolved in ethyl acetate and concentrated by vacuum distillation resulting in crude [R(R*,R*)]-1,1-dimethylethyl 6-cyano-3,5-dihydroxyhexanoate.

後処理

  1. temperaturecooled to −70° C. to −75° C.
  2. additionAfter the addition
  3. temperaturethe reaction mixture is warmed to 15° C. to 25° C.
  4. customquenched by the addition of acetic acid
  5. concentrationconcentrated by vacuum distillation—keeping this distillate
  6. additionThe residue is diluted with methanol
  7. concentrationconcentrated by vacuum distillation—keeping this distillate
  8. customall subsequent ones separate from the first one
  9. dissolutionThe residue is dissolved in a mixture of water and ethyl acetate
  10. customthe layers separated
  11. concentrationthe organic layer is concentrated by vacuum distillation
  12. dissolutionThe residue is dissolved in methanol
  13. concentrationacetic acid and concentrated by vacuum distillation
  14. dissolutionThe residue is dissolved in ethyl acetate
  15. concentrationconcentrated by vacuum distillation

出典と根拠

ORDレコード
ord-3b7fd741493f4a949a72802ed64ad0dd
出典データセット
uspto-grants-2005_11
特許番号
US06962994B2

反応ノート

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