Hydrochloric Acid → (S)-2-((S)-2-tert-butoxycarbonylamino-3-difluoromethoxy-propionylamino)-3-di-fluoromethoxy-propionic acid benzyl ester

HRID 61292

反応式

HRID 61292 の反応式
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][O:14][CH:15]([F:17])[F:16])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[CH2:19]([O:26][C:27](=[O:35])[C@@H:28]([NH2:34])[CH2:29][O:30][CH:31]([F:33])[F:32])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.CN1CCOCC1>ClCCl.C(OCC)(=O)C>[CH2:19]([O:26][C:27](=[O:35])[C@@H:28]([NH:34][C:10](=[O:12])[C@@H:9]([NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:13][O:14][CH:15]([F:17])[F:16])[CH2:29][O:30][CH:31]([F:33])[F:32])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

参加物

9

反応物 6

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86709693(S)-2-tert-Butoxycarbonylamino-3-difluoromethoxy-propionic acidHCID 90040140(S)-2-amino-3-difluoromethoxypropionic acid benzyl ester hydrochloride salt

生成物 1

HCID 90040250(S)-2-((S)-2-tert-butoxycarbonylamino-3-difluoromethoxy-propionylamino)-3-di-fluoromethoxy-propionic acid benzyl ester収率 65.5%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of the compound of Formula IV(a), (S)-2-tert-butoxycarbonylamino-3-difluoromethoxypropionic acid (1.15 g, 4.49 mmol) and the compound of Formula V(a), (S)-2-amino-3-difluoromethoxypropionic acid benzyl ester hydrochloride salt (1.15 g, 4.08 mmol), HOBt (0.689 g, 5.10 mmol) and EDCl.HCl (0.867 g, 5.10 mmol) in dichloromethane (20 mL) was added N-methylmorpholine (0.45 mL, 8.16 mmol) dropwise at 0° C. The reaction mixture was allowed to warm up to room temperature and stirred overnight. The mixture was then diluted with ethyl acetate and washed successively with water, 1N HCl and brine. The organic layer was dried over MgSO4 and concentrated. The crude product was purified by silica-gel column chromatography, eluting with 10% to 12.5% ethyl acetate in hexanes, to give the compound of Formula II(a)(ii), (S)-2-((S)-2-tert-butoxycarbonylamino-3-difluoromethoxy-propionylamino)-3-di-fluoromethoxy-propionic acid benzyl ester (1.29 g, 65%) as an off-white solid. 1H NMR (300 MHz, CDCl3): δ (ppm) 7.35-7.41 (m, 5H), 7.18 (td, 1H), 6.18 (wt, 1H), 6.22 (wt, 1H), 5.25-5.20 (m, 1H), 5.19 (s, 2H), 4.82 (td, 1H), 4.42 (br s, 1H), 4.31 (td, 1H), 4.20-4.15 (m, 2H), 4.01 (dd, 1H), 1.41 (s, 9H).

後処理

  1. washwashed successively with water, 1N HCl and brine
  2. dry with materialThe organic layer was dried over MgSO4
  3. concentrationconcentrated
  4. customThe crude product was purified by silica-gel column chromatography
  5. washeluting with 10% to 12.5% ethyl acetate in hexanes

出典と根拠

ORDレコード
ord-29c31db5892f4c9d8bce00608374965a
出典データセット
uspto-grants-2016_09
特許番号
US09441012B2

関連ノート

読み込み中…