Methanol → (+/-)-9-[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-2,3,6,7,8,9-hexahydro-1H-5-aza-cyclohepta[f]indene-5-carboxylic acid isopropyl ester

HRID 507077Notes

Reaction equation

HRID 507077 reaction equation
[CH:1]([O:4][C:5]([N:7]1[C:20]2[C:12](=[CH:13][C:14]3[CH2:15][CH2:16][CH2:17][C:18]=3[CH:19]=2)[CH:11]([N:21]([CH2:27][C:28]2[CH:33]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:31]=[C:30]([C:38]([F:41])([F:40])[F:39])[CH:29]=2)[C:22]2[N:23]=[N:24][NH:25][N:26]=2)[CH2:10][CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2].CO.[C:44]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>ClCCl>[CH:1]([O:4][C:5]([N:7]1[C:20]2[C:12](=[CH:13][C:14]3[CH2:15][CH2:16][CH2:17][C:18]=3[CH:19]=2)[CH:11]([N:21]([CH2:27][C:28]2[CH:29]=[C:30]([C:38]([F:39])([F:40])[F:41])[CH:31]=[C:32]([C:34]([F:35])([F:36])[F:37])[CH:33]=2)[C:22]2[N:23]=[N:24][N:25]([CH3:44])[N:26]=2)[CH2:10][CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 887Methanol2×HCID 11776Triphenylphosphine2×HCID 220568ethyl N-ethoxycarbonyliminocarbamate2×HCID 11599558(+/-)-9-[(3,5-Bis-trifluoromethyl-benzyl)-(2H-tetrazol-5-yl)-amino]-2,3,6,7,8,9-hexahydro-1H-5-aza-cyclohepta[f]indene-5-carboxylic acid isopropyl Ester

Product 1

HCID 11599660(+/-)-9-[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-2,3,6,7,8,9-hexahydro-1H-5-aza-cyclohepta[f]indene-5-carboxylic acid isopropyl esterYield 51.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (+/−)-isopropyl 9-[(3,5-bis-trifluoromethyl-benzyl)-(2H-tetrazol-5-yl)-amino]-2,3,6,7,8,9-hexahydro-1H-5-aza-cyclohepta[f]indene-5-carboxylate (Example 49) (48 mg, 0.082 mmol) and methanol (0.015 mL, 0.36 mmol) in dichloromethane (1 mL) at room temperature, under nitrogen atmosphere, add triphenyl phosphine (22 mg, 0.082 mmol) in one portion. Add diethyl azodicarboxylate (0.015 mL, 0.082 mmol). The reaction mixture was allowed to stir at room temperature overnight. Add methanol (0.015 mL, 0.36 mmol), triphenyl phosphine (22 mg, 0.082 mmol) and diethyl azodicarboxylate (0.015 mL, 0.082 mmol). After stirring for 6 h, remove the solvents under reduced pressure. Purify the residue by flash chromatography, eluting with hexanes/ethyl acetate, to afford the title compound (25 mg, 51%). MS (ES+): 597 (M+H).

Workup

  1. stirringAfter stirring for 6 h
  2. customremove the solvents under reduced pressure
  3. customPurify the residue by flash chromatography
  4. washeluting with hexanes/ethyl acetate

Sources & evidence

ORD record
ord-856ca4fa28ba43d19e5d9059adff2ed4
Source dataset
uspto-grants-2010_08
Patent number
US07786108B2

Reaction notes

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