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

HRID 1924474Notes

Reaction equation

HRID 1924474 reaction equation
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

Participants

7

Reactant 5

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-b9bfad716a144559b186e08d680799fd
Source dataset
uspto-grants-2012_05
Patent number
US08178552B2

Reaction notes

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