Acetic Acid → (6R,9R)-6-(2,3-difluorophenyl)-3-(dimethylamino)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-ol

HRID 1099180노트

반응식

HRID 1099180 반응식
[C:1]([BH3-])#[N:2].[Na+].N[C:6]1[CH:7]=[C:8]2[CH2:16][C@H:15]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[C:18]=3[F:24])[CH2:14][CH2:13][C@@H:12]([OH:25])[C:9]2=[N:10][CH:11]=1.C=O.[C:28](O)(=O)C>C(#N)C>[F:24][C:18]1[C:19]([F:23])=[CH:20][CH:21]=[CH:22][C:17]=1[C@@H:15]1[CH2:14][CH2:13][C@@H:12]([OH:25])[C:9]2=[N:10][CH:11]=[C:6]([N:2]([CH3:1])[CH3:28])[CH:7]=[C:8]2[CH2:16]1

참가 물질

6

반응물 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 57911417(6R,9R)-3-amino-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-ol

생성물 1

HCID 57911469(6R,9R)-6-(2,3-difluorophenyl)-3-(dimethylamino)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-ol수율 45%

시약·촉매·용매 1

HCID 6342Acetonitrile용매2회

실험 절차

SODIUM CYANOBOROHYDRIDE (242 mg, 3.86 mmol) was added to the Acetonitrile (2 mL) solution of (6R,9R)-3-amino-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-ol (56 mg, 0.193 mmol) and FORMALDEHYDE (1 mL, 13.43 mmol) at rt. The reaction was stirred at room temperature for 4 hours. ACETIC ACID (0.5 mL, 8.73 mmol) was added to the reaction mixture (Caution: heat generation was observed to cause acetonitrile reflux) and the reaction was stirred overnight. Volatile was removed mostly via vacuum and the crude was added NaOH (1N), extracted with ethyl acetate twice. The ethyl acetate layer was dried (Na2SO4), filtered and concentrated. Flash column by methanol in CH2Cl2 from 0 to 4% gave the desired product (27.6 mg, 45%). MS (ESI)[M+H+]=319.35.

후처리

  1. stirringthe reaction was stirred overnight
  2. customVolatile was removed mostly via vacuum
  3. additionthe crude was added NaOH (1N)
  4. extractionextracted with ethyl acetate twice
  5. dry with materialThe ethyl acetate layer was dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated

출처 및 근거

ORD 기록
ord-caf00060cac549809a31a5888ca491cb
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08143403B2

반응 노트

불러오는 중…