Triphenylphosphine → HCID 58318673, compound

HRID 1027930Notes

Reaction equation

HRID 1027930 reaction equation
CCOC(/N=N/C(OCC)=O)=O.[Cl:13][C:14]1[C:23]2[C:18](=[CH:19][C:20]([O:25][CH3:26])=[C:21]([OH:24])[CH:22]=2)[N:17]=[CH:16][N:15]=1.O[C@H:28]1[CH2:33][CH2:32][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[C@H:30]([C:41]([O:43][CH3:44])=[O:42])[CH2:29]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[Cl:13][C:14]1[C:23]2[C:18](=[CH:19][C:20]([O:25][CH3:26])=[C:21]([O:24][C@@H:28]3[CH2:33][CH2:32][N:31]([C:34]([O:36][C:37]([CH3:38])([CH3:39])[CH3:40])=[O:35])[C@H:30]([C:41]([O:43][CH3:44])=[O:42])[CH2:29]3)[CH:22]=2)[N:17]=[CH:16][N:15]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 7010734(2S,4S)-1-tert-butyl 2-methyl-4-hydroxypiperidine-1,2-dicarboxylateHCID 231324754-Chloro-7-methoxyquinazolin-6-ol

Product 1

HCID 58318673HCID 58318673, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of DEAD (0.329 ml, 2.08 mmol) in DCM (2 ml) was added to as stirred suspension of 4-chloro-7-methoxyquinazolin-6-ol (283 mg, 1.74 mmol prepared as described in Example 16 of WO03/082831),1-tert-butyl 2-methyl (2S,4S)-4-hydroxypiperidine-1,2-dicarboxylate (11) (450 mg, 2.08 mmol) and triphenylphosphine (547 mg, 2.098 mmol) in DCM (10 ml), such that the internal temperature remained <30° C. The reaction mixture was stirred overnight and evaporated to dryness. The residues were purified by column chromatography on SiO2 eluting with increasingly polar mixtures of DCM/methanol (100/0-95/5). The fractions containing the desired product were combined and evaporated to give 1-tert-butyl 2-methyl (2S,4R)-4-[(4-chloro-7-methoxyquinazolin-6-yl)oxy]piperidine-1,2-dicarboxylate (12) as a gum (478 mg, 79%): 1H NMR Spectrum: (DMSO-d6) δ1.39-1.46 (10H, m), 1.73-1.84 (1H, m), 1.92-2.03 (1H, m), 2.10-2.18 (1H, m), 2.60-2.69 (1H, m), 3.15-3.40 (3H, m), 3.74-3.85 (1H, m), 4.01 (3H, s), 4.61-4.73 (1H, m), 5.06 (1H, s), 7.43 (1H, s), 7.47 (1H, s), 8.89 (1H, s), 8.97 (1H, s); Mass Spectrum: (M+H)+ 452.

Workup

  1. customprepared
  2. customremained <30° C
  3. stirringThe reaction mixture was stirred overnight
  4. customevaporated to dryness
  5. customThe residues were purified by column chromatography on SiO2 eluting
  6. temperaturewith increasingly polar mixtures of DCM/methanol (100/0-95/5)
  7. additionThe fractions containing the desired product
  8. customevaporated

Sources & evidence

ORD record
ord-44b4e0194bc749a696bccebf9b4a8ae7
Source dataset
uspto-grants-2014_05
Patent number
US08735410B2

Reaction notes

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