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

HRID 552259ノート

反応式

HRID 552259 の反応式
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][CH:23](N3CCOCC3)[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

参加物

7

反応物 5

HCID 176Acetic AcidHCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 230902141,4-Oxazepane hydrochlorideHCID 534863564-(1,4-Dioxaspiro[4.5]decan-8-yl)morpholine

生成物 1

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

試薬・触媒・溶媒 1

HCID 111,2-Dichloroethane溶媒

実験手順

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 ketone 1 (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 AcOEt (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 3 (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).

後処理

  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

出典と根拠

ORDレコード
ord-23d305d431ab494bb9374285e875a0e1
出典データセット
uspto-grants-2011_05
特許番号
US07951802B2

反応ノート

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