Acetic Acid → 4-(1,4-Dioxaspiro[4.5]dec-8-yl)hexahydro-1,4-oxazepine

HRID 1924474노트

반응식

HRID 1924474 반응식
CCN(CC)CC.[CH2:8]1[CH2:14][O:13][CH2:12][CH2:11][NH:10][CH2:9]1.Cl.[O:16]1[C:20]2([CH2:25][CH2:24][C:23](=O)[CH2:22][CH2:21]2)[O:19][CH2:18][CH2:17]1.C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl>[O:16]1[C:20]2([CH2:25][CH2:24][CH:23]([N:10]3[CH2:9][CH2:8][CH2:14][O:13][CH2:12][CH2:11]3)[CH2:22][CH2:21]2)[O:19][CH2:18][CH2:17]1

참가 물질

7

반응물 5

HCID 176Acetic AcidHCID 8471TriethylamineHCID 5674151,4-Dioxaspiro[4.5]decan-8-oneHCID 5049666Sodium triacetoxyborohydrideHCID 230902141,4-Oxazepane hydrochloride

생성물 1

HCID 592386344-(1,4-Dioxaspiro[4.5]dec-8-yl)hexahydro-1,4-oxazepine수율 101.9%

시약·촉매·용매 1

HCID 111,2-Dichloroethane용매

실험 절차

Et3N (96.9 mL, 0.695 mol) was added in one portion to a stirred suspension of homomorpholine hydrochloride (79.76 g, 0.579 mol) and 1,4-dioxaspiro[4.5]decan-8-one (90.5 g, 0.579 mol) in 1,2-dichloroethane (1.81 L). Then glacial acetic acid (34.8 mL, 0.607 mol) was added in one portion followed by solid NaBH(OAc)3 (154 g, 0.727 mol) in one portion as well. This was accompanied by 5° C. increase in the temperature of the reaction mixture. After 2 h 45 min the reaction was quenched by addition of 10% aqueous NaOH (800 mL). The mixture was stirred for 10 min. The organic layer was separated, washed with brine (100 mL), dried (MgSO4) and concentrated to afford an oil (142.36 g) with some suspended solid, which was filtered off (3.00 g). The aqueous part of the reaction mixture was combined with the brine washings and extracted with EtOAc (4×500 mL). Combined extracts were washed with brine (100 mL), dried (MgSO4) and concentrated to afford additional portion of oil (16.82 g). The two oily products were combined and distilled in vacuum to give 8 (101.07 g, 72%) as colorless liquid, b.p. 122° C./8.9·10−3 mbar. 1H NMR (400 MHz, CDCl3) δ 1.48-1.64 (m, 4H), 1.70-1.88 (m, 6H), 2.50-2.63 (m, 1H), 2.71-2.81 (m, 4H), 3.66-3.72 (m, 2H), 3.78 (t, J=6.0 Hz, 2H), 3.93 (s, 4H).

후처리

  1. customThis was accompanied by 5° C.
  2. temperatureincrease in the temperature of the reaction mixture
  3. customAfter 2 h 45 min the reaction was quenched by addition of 10% aqueous NaOH (800 mL)
  4. customThe organic layer was separated
  5. washwashed with brine (100 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated

출처 및 근거

ORD 기록
ord-b9bfad716a144559b186e08d680799fd
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08178552B2

반응 노트

불러오는 중…