Trimethyl phosphonoacetate → HCID 53716603, compound

HRID 351477Notes

Reaction equation

HRID 351477 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH3:11][O:12][C:13]([CH2:15]P(OC)(OC)=O)=[O:14].[C:22]([O:26][C:27]([N:29]1[CH2:34][CH2:33][NH:32][C:31]([CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)([CH:35]=O)[CH2:30]1)=[O:28])([CH3:25])([CH3:24])[CH3:23].C(OC(N1CCNC(CC2C=CC(F)=CC=2F)(C=O)C1)=O)(C)(C)C.COC(C1(CC2C=CC=CC=2)C(=NO)CCN(CC2C=CC=CC=2)C1)=O>C(Cl)Cl.CCOC(C)=O.O.C1COCC1>[C:22]([O:26][C:27]([N:29]1[CH2:34][CH2:33][NH:32][C:31]([CH2:37][C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)([CH:35]=[CH:15][C:13]([O:12][CH3:11])=[O:14])[CH2:30]1)=[O:28])([CH3:23])([CH3:24])[CH3:25]

Participants

10

Reactant 5

HCID 80029Trimethyl phosphonoacetateHCID 2724254Sodium bis(trimethylsilyl)amideHCID 54066206HCID 54066206, compoundHCID 54233415HCID 54233415, compoundHCID 76529594HCID 76529594, compound3×

Product 1

HCID 53716603HCID 53716603, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a THF (1 mL) solution of NaHMDS at 0° C. was added trimethyl phosphonoacetate (0.18 mL, 1.1 mmol), dropwise. After stirring for 1 hour, a THF (1 mL) solution of crude 3-benzyl-3-formyl-piperazine-1-carboxylic acid tert-butyl ester (0.34 mg, 0.92 mmol), prepared analogous to the compound of Example 198, Step A, was added and the reaction was allowed to warm to room temperature. After stirring for 16 hours, the product was isolated by extraction from water with EtOAc (2×) and methylene chloride (2×). The combined extracts were washed with brine, dried (MgSO4) and concentrated. The product was then purified by silica gel chromatography using methylene chloride, then 5% MeOH in methylene chloride as eluents to afford a 7:3 E:Z mixture of olefins of the compound of Example 201, Step A (0.38 g, 81%), where the Z isomer had lactamized: +APcl MS (M+1, ester)+ 361, (M-tButyl+1, ester)+ 305, (M-tBu+1, lactam)+ 273, (M-BOC+1, ester)+ 261, (M-BOC+1, lactam)+ 229; 1H NMR (400 MHz, CDCl3) δ: 7.30-7.05 (arom, series of m, 5 H), 6.91 (lactam olefin, d, 0.3H), 6.75 (ester olefin, d, 0.7H), 6.09 (lactam olefin, d, 0.3H), 5.88 (ester olefin, d, 0.7H), 3.71 (ester Me, s 2.1H), 1.47 (BOC, s, 9H).

Workup

  1. additionwas added
  2. stirringAfter stirring for 16 hours
  3. washThe combined extracts were washed with brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customThe product was then purified by silica gel chromatography
  7. custom5% MeOH in methylene chloride as eluents to afford a 7:3 E

Sources & evidence

ORD record
ord-3d33194ebe984143ab45527177ca8408
Source dataset
uspto-grants-2004_06
Patent number
USRE038524E1

Reaction notes

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