Sodium Hydroxide → methyl 3-(S)-((2-methoxy-5-(1-tetrazolyl)phenyl)methylamino)-2-(S)-(4-fluorophenyl)cyclopentane-1-(S)-carboxylate

HRID 1289967Notes

Reaction equation

HRID 1289967 reaction equation
[NH2:1][C@H:2]1[CH2:6][CH2:5][C@H:4]([C:7]([O:9][CH3:10])=[O:8])[C@H:3]1[C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1.[CH3:18][O:19][C:20]1[CH:27]=[CH:26][C:25]([N:28]2[CH:32]=[N:31][N:30]=[N:29]2)=[CH:24][C:21]=1[CH:22]=O.C([BH3-])#N.[Na+].[OH-].[Na+]>CO.O.C(O)(=O)C>[CH3:18][O:19][C:20]1[CH:27]=[CH:26][C:25]([N:28]2[CH:32]=[N:31][N:30]=[N:29]2)=[CH:24][C:21]=1[CH2:22][NH:1][C@H:2]1[CH2:6][CH2:5][C@H:4]([C:7]([O:9][CH3:10])=[O:8])[C@H:3]1[C:11]1[CH:12]=[CH:13][C:14]([F:17])=[CH:15][CH:16]=1

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 5003444Sodium cyanoborohydrideHCID 105361692-Methoxy-5-tetrazol-1-yl-benzaldehydeHCID 22885811Methyl 3-(S)-(amino)-2-(S)-(4-fluorophenyl)cyclopentane-1-(S)-carboxylate

Product 1

HCID 67592890methyl 3-(S)-((2-methoxy-5-(1-tetrazolyl)phenyl)methylamino)-2-(S)-(4-fluorophenyl)cyclopentane-1-(S)-carboxylateYield 55.8%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a solution of 100 mg of amine from Example 63 in 2 mL of methanol was added 0.040 mL of acetic acid, 1 g of 3A sieves and 94 mg 2-methoxy-5-(1-tetrazolyl)benzaldehyde (prepared according to the procedures given in PCT International Application WO 95/08549, published 30 Mar. 1995; p. 33). The reaction was stirred at room temperature for 30 min and then 0.080 g of sodium cyanoborohydride was added. The reaction was stirred further for 20 h and was then poured into water, made basic with 2N NaOH and extracted twice with ether. The organic layers were washed with a portion of brine, combined, dried over sodium sulfate and evaporated. The residue was purified by flash chromatography eluting with 0 to 3% methanol in methylene chloride to obtain 100 mg of title compound. NMR (CDCl3): δ 1.5 (br s, NH/H2O), 1.8-1.9 (m, 1H), 1.9-2.05 (m, 2H), 2.2-2.35 (m, 1H), 2.24 (m, 1H), 3.3-3.45 (m, 1H), 3.45-3.55 (m, 2H), 3.59 (s, 3H), 3.63 (s, 3H), 3.68 (d, 1H), 6.86 (d, 1H), 6.98 (t, 2H), 7.17 (m, 2H), 7.36 (d, 1H), 7.46 (dd, 1H), 8.85 (s, 1H).

Workup

  1. customprepared
  2. stirringThe reaction was stirred further for 20 h
  3. extractionextracted twice with ether
  4. washThe organic layers were washed with a portion of brine
  5. dry with materialdried over sodium sulfate
  6. customevaporated
  7. customThe residue was purified by flash chromatography
  8. washeluting with 0 to 3% methanol in methylene chloride

Sources & evidence

ORD record
ord-439fadf3feea418f88194dfca07db8d2
Source dataset
uspto-grants-1998_05
Patent number
US05750549

Reaction notes

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