Phosgene → HCID 22954557, compound

HRID 2230457Notes

Reaction equation

HRID 2230457 reaction equation
[N:1]1([C:14]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:15])[CH2:6][CH2:5][CH2:4][C@@H:3]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[NH:2]1.C(N(C(C)C)CC)(C)C.[C:33](Cl)(Cl)=[O:34].[C:37]([NH:45][NH:46][CH2:47][CH2:48][C:49]([O:51][CH2:52][C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1)=[O:50])(=[O:44])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>CCCCCC.CCOC(C)=O.C1(C)C=CC=CC=1>[C:37]([NH:45][N:46]([CH2:47][CH2:48][C:49]([O:51][CH2:52][C:53]1[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=1)=[O:50])[C:33]([N:2]1[C@H:3]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:4][CH2:5][CH2:6][N:1]1[C:14]([O:16][CH2:17][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)=[O:15])=[O:34])(=[O:44])[C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1

Participants

8

Reactant 4

HCID 6371PhosgeneHCID 81531Diisopropylethylamine2×HCID 110345581-Benzyl 3-tert-butyl (3S)-tetrahydropyridazine-1,3(2H)-dicarboxylateHCID 18465756HCID 18465756, compound

Product 1

HCID 22954557HCID 22954557, compoundYield 89%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolvent2×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (3S)-1-benzyl 3-t-butyl hexahydropyridazine-1,3-dicarboxylate (Hassall et al. J. Chem. Soc. Perkin 1, pp. 1451-1454 (1979)) (925.3 mg, 2.89 mmol) and diisopropylethylamine (0.70 ml, 4.0 mmol) in a 1.93M toluene solution of phosgene (17.96 ml, 34.7 mmol) was stirred at room temperature for 45 min then concentrated to leave a yellow solid. To this solid was added toluene (18 ml), hydrazide (259) (861.6 mg, 2.89 mmol) and diisopropylethylamine (0.70 ml, 4.0 mmol). The mixture was stirred at room temperature for 2.75 h, then concentrated. The resulting residue was taken up in EtOAc, washed twice with 1M HCl, brine, then dried (MgSO4), filtered and concentrated to afford 2.15 g of crude material. flash chromatography (40% EtOAc in hexane) afforded 1.65 g (89%) of the title compound as a white foam: mp 30° C.; [α]D24 −55.78° (c 0.40, CH2Cl2); IR (KBr) 3436, 2930, 1733, 1689, 1455, 1412 1367, 1258, 1156, 697; 1H NMR (CDCl3) δ8.54-8.23 (0.5H, m), 7.97-7.09 (15.5H), 5.16-4.80 (4H, m), 4.66-4.32 (1H, m), 4.24-3.55 (3.3H, m), 3.50-3.26 (0.4H, m), 3.19-2.49 (2.3H, m), 2.11-1.43 (6H, m), 1.32-1.05 (7H, m); Anal. Calcd for C35H40N4O8.0.5H2O: C, 64.31; H, 6.32; N, 8.57. Found: C, 64.18; H, 6.27; N, 8.56. MS (ES+) 662 (M+Na, 84%), 645 (M++1, 100), 384 (77).

Workup

  1. concentrationthen concentrated
  2. customto leave a yellow solid
  3. concentrationconcentrated
  4. washwashed twice with 1M HCl, brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto afford 2.15 g of crude material

Sources & evidence

ORD record
ord-7fc444ea6eb74044ad5d75fedbd8399b
Source dataset
uspto-grants-2002_07
Patent number
US06423840B1

Reaction notes

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