Sodium Bicarbonate → Benzyl 4-(4-{2-[2-(4-fluorophenyl)ethylamino]ethoxy}phenyl)-3-[4-(3-methoxypropyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]piperidine-1-carboxylate

HRID 1176601노트

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HRID 1176601 반응식
[NH2:1][CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([CH:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[O:18])[CH2:13][CH:12]2[O:27][CH2:28][C:29]2[CH:30]=[CH:31][C:32]3[O:37][CH2:36][CH2:35][N:34]([CH2:38][CH2:39][CH2:40][O:41][CH3:42])[C:33]=3[CH:43]=2)=[CH:7][CH:6]=1.[F:44][C:45]1[CH:50]=[CH:49][C:48]([CH2:51][CH:52]=O)=[CH:47][CH:46]=1.C([O-])(=O)C.[Na+].C([BH3-])#N.[Na+].C(=O)([O-])O.[Na+]>O1CCCC1.CO>[F:44][C:45]1[CH:50]=[CH:49][C:48]([CH2:51][CH2:52][NH:1][CH2:2][CH2:3][O:4][C:5]2[CH:6]=[CH:7][C:8]([CH:11]3[CH2:16][CH2:15][N:14]([C:17]([O:19][CH2:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)=[O:18])[CH2:13][CH:12]3[O:27][CH2:28][C:29]3[CH:30]=[CH:31][C:32]4[O:37][CH2:36][CH2:35][N:34]([CH2:38][CH2:39][CH2:40][O:41][CH3:42])[C:33]=4[CH:43]=3)=[CH:9][CH:10]=2)=[CH:47][CH:46]=1

참가 물질

8

반응물 5

HCID 516892Sodium BicarbonateHCID 517045Sodium AcetateHCID 5003444Sodium cyanoborohydrideHCID 111263222-(4-Fluorophenyl)acetaldehydeHCID 68501706benzyl 4-[4-(2-aminoethoxy)phenyl]-3-[4-(3-methoxypropyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]piperidine-1-carboxylate

생성물 1

HCID 68500702Benzyl 4-(4-{2-[2-(4-fluorophenyl)ethylamino]ethoxy}phenyl)-3-[4-(3-methoxypropyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]piperidine-1-carboxylate

시약·촉매·용매 2

HCID 887Methanol용매2회HCID 8028Tetrahydrofuran용매2회

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온도
20 °C

실험 절차

0.361 g of benzyl 4-[4-(2-aminoethoxy]phenyl]-3-[4-(3-methoxypropyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]piperidine-1-carboxylate (Example 184) is dissolved under argon in tetrahydrofuran. 2 g of 4 Å molecular sieve are added, followed by a solution of (4-fluorophenyl)acetaldehyde in 1 ml of tetrahydrofuran. The reaction mixture is stirred at 20° C. for 2 hours. 3 ml of methanol and 0.078 g of sodium acetate are added to the mixture. A solution of 0.055 g of sodium cyanoborohydride in 3 ml of methanol is added dropwise at 0° C. and the mixture is subsequently stirred at 0° C. over 1 hour. 10 ml of saturated aqueous sodium hydrogencarbonate solution are added and the mixture is subsequently filtered through Hyflo. The filtrate is extracted with ethyl acetate (2×20 ml)—the combined organic phases are washed with 20 ml of brine, dried over sodium sulphate and concentrated by evaporation. The title compound is obtained from the residue by means of flash chromatography (SiO2 60F). Rf=0.20 (200:5:1 dichloromethane-methanol-25% conc. ammonia); Rt=4.74.

후처리

  1. addition2 g of 4 Å molecular sieve are added
  2. stirringthe mixture is subsequently stirred at 0° C. over 1 hour
  3. filtrationthe mixture is subsequently filtered through Hyflo
  4. extractionThe filtrate is extracted with ethyl acetate (2×20 ml)—the combined organic phases
  5. washare washed with 20 ml of brine
  6. dry with materialdried over sodium sulphate
  7. concentrationconcentrated by evaporation

출처 및 근거

ORD 기록
ord-20b932198c1c478aa86fb0927391393c
출처 데이터셋
uspto-grants-2010_11
특허 번호
US07842688B2

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