Acetic Acid → (9-(2,3-Difluoro-5-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(5-methylthiophen-2-yl)methanone

HRID 1689266노트

반응식

HRID 1689266 반응식
FC(F)(F)C(O)=O.[CH3:8][C:9]1[S:13][C:12]([C:14]([N:16]2[CH2:21][C:20]3([CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)[O:19][CH2:18][CH2:17]2)=[O:15])=[CH:11][CH:10]=1.[F:27][C:28]1[C:35]([F:36])=[CH:34][C:33]([CH2:37][CH2:38][OH:39])=[CH:32][C:29]=1[CH:30]=O.C(O)(=O)C.C([BH3-])#N.[Na+]>CO>[F:27][C:28]1[C:35]([F:36])=[CH:34][C:33]([CH2:37][CH2:38][OH:39])=[CH:32][C:29]=1[CH2:30][N:24]1[CH2:25][CH2:26][C:20]2([O:19][CH2:18][CH2:17][N:16]([C:14]([C:12]3[S:13][C:9]([CH3:8])=[CH:10][CH:11]=3)=[O:15])[CH2:21]2)[CH2:22][CH2:23]1

참가 물질

6

반응물 4

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 579891022,3-Difluoro-5-(2-hydroxyethyl)benzaldehydeHCID 67292300(5-Methylthiophen-2-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate

생성물 1

HCID 57988906(9-(2,3-Difluoro-5-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(5-methylthiophen-2-yl)methanone

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

(5-Methylthiophen-2-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate (example 9, step b) (0.53 g) was added to a solution of 2,3-difluoro-5-(2-hydroxyethyl)benzaldehyde (example 32, step b) (0.25 g) and acetic acid (0.08 mL) in methanol (5 mL). The reaction was stirred for 30 min and cooled in an ice bath. Sodium cyanoborohydride (0.13 g) was then added, the mixture allowed to warm to RT and stirred for 18 h. The reaction was concentrated in vacuo. Purification was by silica gel chromatography eluting with 99:1:0.1 to 97:3:0.3 DCM:methanol:‘880’ aqueous ammonia gradient. The fractions containing product were combined and evaporated in vacuo to give the subtitled compound as a gum. Yield 0.08 g.

후처리

  1. temperaturecooled in an ice bath
  2. stirringstirred for 18 h
  3. concentrationThe reaction was concentrated in vacuo
  4. customPurification
  5. washeluting with 99:1:0.1 to 97:3:0.3 DCM
  6. additionThe fractions containing product
  7. customevaporated in vacuo

출처 및 근거

ORD 기록
ord-2da91e6e49134390b783d02336e98a1c
출처 데이터셋
uspto-grants-2012_04
특허 번호
US08148373B2

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