Cyproheptadine → HCID 15454921, compound

HRID 2287535Notes

Reaction equation

HRID 2287535 reaction equation
[NH2:1][C@H:2]1[CH2:7][C@@H:6]([C:8]([O:10][CH3:11])=[O:9])[CH2:5][N:4]([C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:13])[C@H:3]1[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.[CH3:28][O:29][C:30]1[CH:37]=[CH:36][C:35]([O:38][C:39]([F:42])([F:41])[F:40])=[CH:34][C:31]=1[CH:32]=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].CN1CCC(=C2C3C(=CC=CC=3)C=CC3C2=CC=CC=3)CC1.C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl>[CH2:15]([O:14][C:12]([N:4]1[CH2:5][C@H:6]([C:8]([O:10][CH3:11])=[O:9])[CH2:7][C@H:2]([NH:1][CH2:32][C:31]2[CH:34]=[C:35]([O:38][C:39]([F:40])([F:41])[F:42])[CH:36]=[CH:37][C:30]=2[O:29][CH3:28])[C@@H:3]1[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:13])[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

7

Reactant 5

HCID 2913CyproheptadineHCID 10340Sodium CarbonateHCID 27833642-Methoxy-5-(trifluoromethoxy)benzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 15454919HCID 15454919, compound

Product 1

HCID 15454921HCID 15454921, compoundYield 114.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (2S*,3S*,5R*)-3-amino-1-benzyloxycarbonyl-5-methoxycarbonyl-2-phenylpiperidine (0.84 g, 2.28 mmol) and 2-methoxy-5-trifluoromethoxybenzaldehyde (0.63 g, 2.85 mmol) in CH2Cl2 (18.0 ml) was added NaB(OAc)3H (0.73 g, 3.42 mmol) potionwise at room temperature. After the turbid reactin mixture was stirred vigorously at room temperature for 4 hours, sat. Na2CO3 aq. solution (15.0 ml) was added to make the mixture to be basic (pH10-11). The CH2Cl2 layer was separated from the mixture, and the aqueous layer was extracted with CH2Cl2 (×4). The combined CH2Cl layer and extracts were dried (Na2SO4), and concentrated in vacuo to give a viscous pale yellow oil (1.49 g). This was chromatographed over SiO2 (Merck Kieselgel 60, 30.0 g). Elution with CH2Cl2 --MeOH (300:1/250:1) gave title compound (1.26 g, 96.2%) as a viscous colorless oil. IR νmax (film): 3450(w), 3330(w), 1740(shoulder, s), 1735(s), 1703(s), 1700(s), 1687(s), 1610(w), 1497(s), 1160(br., s), 1030(s), 815(m), 765(s), 740(s), 700(s) cm-1 ; 1H-NMR δ: 7.65-7.50(m, 1H), 7.52-7.38(m, 1H), 7.40-7.11(m, 8H), 7.2-6.96(m, 2H), 6.74(br.d, J=8.8 Hz, 1H), 5.45-5.34(m, 0.5H), 5.20-5.00(m, 2H), 5.17-5.05(m, 0.5H), 4.49-4.33(m, 0.5H), 4.35-4.17(m, 0.5H), 3.90-3.53(m, 2H), 3.69(br.s, 6H), 3.20(br.dd, J=13.2, 13.2 Hz, 1H), 3.20-3.00(m, 1H), 2.83-2.60(m, 1H), 2.26-1.99(m,2H), 1.52(br.s, 1H) ppm.

Workup

  1. customThe CH2Cl2 layer was separated from the mixture
  2. extractionthe aqueous layer was extracted with CH2Cl2 (×4)
  3. dry with materialThe combined CH2Cl layer and extracts were dried (Na2SO4)
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-eecf6da9b826474bbb45acb68b85ec0d
Source dataset
uspto-grants-2000_07
Patent number
US06083943

Reaction notes

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