Acetic Acid → N-[(1S)-1-[4-[[4-(1,1-Dimethylethyl)-1-piperidinyl]methyl]phenyl]-2,2,2-trifluoroethyl]methanesulfonamide

HRID 1518981ノート

反応式

HRID 1518981 の反応式
Cl.[C:2]([CH:6]1[CH2:11][CH2:10][NH:9][CH2:8][CH2:7]1)([CH3:5])([CH3:4])[CH3:3].C(N(CC)CC)C.[F:19][C:20]([F:36])([F:35])[C@@H:21]([NH:30][S:31]([CH3:34])(=[O:33])=[O:32])[C:22]1[CH:27]=[CH:26][C:25]([CH:28]=O)=[CH:24][CH:23]=1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>C(Cl)Cl>[C:2]([CH:6]1[CH2:11][CH2:10][N:9]([CH2:28][C:25]2[CH:24]=[CH:23][C:22]([C@H:21]([NH:30][S:31]([CH3:34])(=[O:33])=[O:32])[C:20]([F:35])([F:36])[F:19])=[CH:27][CH:26]=2)[CH2:8][CH2:7]1)([CH3:5])([CH3:4])[CH3:3]

参加物

8

反応物 6

HCID 176Acetic AcidHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 27946764-tert-butylpiperidine HydrochlorideHCID 5049666Sodium triacetoxyborohydrideHCID 86691246HCID 86691246、化合物

生成物 1

HCID 71655815N-[(1S)-1-[4-[[4-(1,1-Dimethylethyl)-1-piperidinyl]methyl]phenyl]-2,2,2-trifluoroethyl]methanesulfonamide収率 62%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

Charge a five liter round-bottom flask with DCM (1.5 L) and 4-tert-butylpiperidine hydrochloride (89 g, 0.5 mol). Add triethylamine (101.4 g, 1.0 mol) to the mixture at 21° C. followed by N-[(1S)-2,2,2-trifluoro-1-(4-formylphenyl)ethyl]methanesulfonamide (155 g, 0.55 mol), and acetic acid (36 g, 0.6 mol). Add sodium triacetoxyborohydride (318.6 g, 1.5 mol) portion-wise and stir the suspension at 22° C. for 15 hours. Add saturated aqueous solution of sodium bicarbonate (1800 mL) slowly with stirring until pH of the mixture is 8. Separate the organic layer and extract the aqueous layer with DCM (3×2000 mL). Dry the combined organic layers over MgSO4; filter; collect the filtrate; and concentrate the filtrate under vacuum. Purify the residue on silica gel column chromatography eluting with DCM:MeOH (100 to 95%) to provide the title compound as an off-white solid (126 g, 61.9%). MS (m/z): 407 (M+1).

後処理

  1. customat 21° C.
  2. customSeparate the organic layer
  3. extractionextract the aqueous layer with DCM (3×2000 mL)
  4. dry with materialDry the combined organic layers over MgSO4
  5. filtrationfilter
  6. customcollect the filtrate
  7. concentrationand concentrate the filtrate under vacuum
  8. customPurify the residue on silica gel column chromatography
  9. washeluting with DCM

出典と根拠

ORDレコード
ord-ff13d3e852b04bca8c465dee29d58174
出典データセット
uspto-grants-2015_07
特許番号
US09073856B2

反応ノート

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