4-Methylmorpholine → HCID 53650549, compound

HRID 482105Notes

Reaction equation

HRID 482105 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([O:15][S:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[Cl:25])(=[O:18])=[O:17])[CH:5]=[CH:6][C:7]=1[CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[C:26]([O:30][C:31]([N:33]1[CH2:38][CH2:37][CH:36]([CH2:39]O)[CH2:35][CH2:34]1)=[O:32])([CH3:29])([CH3:28])[CH3:27].CN1CCOCC1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[C:26]([O:30][C:31]([N:33]1[CH2:38][CH2:37][CH:36]([CH2:39][O:1][C:2]2[CH:3]=[C:4]([O:15][S:16]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[Cl:25])(=[O:18])=[O:17])[CH:5]=[CH:6][C:7]=2[CH2:8][C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:35][CH2:34]1)=[O:32])([CH3:29])([CH3:27])[CH3:28]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 2764081Tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylateHCID 54456794HCID 54456794, compound

Product 1

HCID 53650549HCID 53650549, compoundYield 84.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To 294 mg (0.787 mmol) of 2-chlorobenzenesulfonic acid 3-hydroxy-4-benzylphenyl ester, as prepared in the preceding step, in tetrahydrofuran (5 mL) containing 236 μL (1.10 mmol) of N-tert-butoxycarbonyl-4-piperidinemethanol, as prepared in step f of Example 1, 300 μL (2.72 mmol) of N-methylmorpholine, and 309 mg (1.18 mmol) of triphenylphosphine was added 185 μL (1.18 mmol) of diethyl azodicarboxylate. The reaction mixture was stirred at ambient temperature for 1 h, quenched with saturated NaHCO3, and extracted into ether. The organic phase was dried (MgSO4) and concentrated in vacuo. Purification by flash chromatography (ethyl acetate/hexane (1:2)) gave 382 mg of the title compound as a colorless foam. 1H-NMR (300 MHz, CDCl3) δ 7.95 (dd, 1H, J=1.5, 8 Hz), 7.55-7.64 (m, 2H), 7.35-7.40 (m, 1H), 7.08-7.26 (m, 5H), 6.93 (d, 2H, J=8 Hz), 6.65 (d, 2 Hz), 6.53 (dd, 1H, J=2, 8 Hz), 3.87 (s, 2H), 3.67 (d, 2H, 6 Hz), 2.69 (t, 2H, J=13 Hz), and 1.47 (s, 9H). Mass spectrum (MALDI-TOF; gentisic acid matrix) calcd. for C30H34ClNO6S: 594.2 (M+Na). Found: 594.0, 472.0 (M - (tert-butoxycarbonyl)+H).

Workup

  1. customquenched with saturated NaHCO3
  2. extractionextracted into ether
  3. dry with materialThe organic phase was dried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customPurification by flash chromatography (ethyl acetate/hexane (1:2))

Sources & evidence

ORD record
ord-f18bb9904f5a465288f01a01d6aaa126
Source dataset
uspto-grants-1998_08
Patent number
US05792769

Reaction notes

Loading…