rac-(7aR,11aR)-N-(diphenylmethylene)-11a-vinyl-7,7a,8,10,11,11a-hexahydro-6H-spiro[dibenzo[b,d]oxepine-9,2'-[1,3]dioxolan]-3-amine → rac-(7aR,11aS)-11a-ethyl-7,7a,8,10,11,11a-hexahydro-6H-spiro[dibenzo[b,d]oxepine-9,2'-[1,3]dioxolan]-3-amine

HRID 718827Notes

Reaction equation

HRID 718827 reaction equation
C1(C(C2C=CC=CC=2)=[N:8][C:9]2[CH:10]=[CH:11][C:12]3[C:18]4([CH:27]=[CH2:28])[CH2:19][CH2:20][C:21]5([CH2:26][CH:17]4[CH2:16][CH2:15][O:14][C:13]=3[CH:29]=2)[O:25][CH2:24][CH2:23][O:22]5)C=CC=CC=1>[Pd].CCO>[CH2:27]([C:18]12[CH2:19][CH2:20][C:21]3([O:25][CH2:24][CH2:23][O:22]3)[CH2:26][CH:17]1[CH2:16][CH2:15][O:14][C:13]1[CH:29]=[C:9]([NH2:8])[CH:10]=[CH:11][C:12]2=1)[CH3:28]

Participants

4

Reactant 1

HCID 86722435rac-(7aR,11aR)-N-(diphenylmethylene)-11a-vinyl-7,7a,8,10,11,11a-hexahydro-6H-spiro[dibenzo[b,d]oxepine-9,2'-[1,3]dioxolan]-3-amine

Product 1

HCID 86722434rac-(7aR,11aS)-11a-ethyl-7,7a,8,10,11,11a-hexahydro-6H-spiro[dibenzo[b,d]oxepine-9,2'-[1,3]dioxolan]-3-amineYield 97.5%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

A 500 mL round-bottom flask equipped with a 3-way stopcock was charged with rac-(7 aS,11aS)—N-(diphenylmethylene)-11a-vinyl-7,7a,8,10,11,11a-hexahydro-6H-spiro[dibenzo[b,d]oxepine-9,2′-[1,3]dioxolan]-3-amine (85, R2=Vinyl) (17.7 g, 38.0 mmol) and 10% palladium on carbon (2.02 g, 1.90 mmol) in EtOH (190 mL). The vessel was evacuated and backfilled with hydrogen from a balloon and the resulting suspension was allowed to stir at rt for about 22 h. The mixture was filtered through a pad of Celite® using rinses of EtOAc (3×25 mL). The combined filtrates were concentrated under reduced pressure and the resulting crude material was purified on silica gel (330 g, eluted with 0 to 50% EtOAc in heptane). Collection and concentration of the appropriate fractions gave rac-(7aR,11aS)-11a-ethyl-7,7a,8,10,11,11a-hexahydro-6H-spiro[dibenzo[b,d]oxepine-9,2′-[1,3]dioxolan]-3-amine (86, R2=Ethyl) (11.24 g, 97%). LC/MS, method 3, 2.14 min, MS m/z 304 (M+H)+. 1H NMR (400 MHz, CDCL3) δ 7.00 (d, J=8.4 Hz, 1H), 6.56-6.45 (m, 2H), 5.34 (bs, 1H), 4.21-4.11 (m, 1H), 3.98-3.85 (m, 4H), 3.72-3.60 (m, 1H), 2.69-2.56 (m, 1H), 2.34-2.24 (m, 1H), 2.19-2.03 (m, 2H), 1.93-1.80 (m, 1H), 1.79-1.65 (m, 2H), 1.64-1.36 (m, 4H), 1.35-1.25 (m, 1H), 0.61 (t, J=7.4 Hz, 3H).

Workup

  1. customA 500 mL round-bottom flask equipped with a 3-way stopcock
  2. customThe vessel was evacuated
  3. filtrationThe mixture was filtered through a pad of Celite®
  4. concentrationThe combined filtrates were concentrated under reduced pressure
  5. customthe resulting crude material was purified on silica gel (330 g, eluted with 0 to 50% EtOAc in heptane)
  6. customCollection and concentration of the appropriate fractions

Sources & evidence

ORD record
ord-a7eba5b6850549c395767c42e14e09e2
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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