Acetic Acid → (S)-5-(9-[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-1,3,6,7,8,9-hexahydro-2-oxa-5-aza-cyclohepta[f]inden-5-yl)-3,3-dimethyl-pentanoic acid methyl ester

HRID 507099Notes

Reaction equation

HRID 507099 reaction equation
[F:1][C:2]([F:36])([F:35])[C:3]1[CH:4]=[C:5]([CH:28]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:30]=1)[CH2:6][N:7]([C@@H:14]1[C:20]2=[CH:21][C:22]3[CH2:23][O:24][CH2:25][C:26]=3[CH:27]=[C:19]2[NH:18][CH2:17][CH2:16][CH2:15]1)[C:8]1[N:9]=[N:10][N:11]([CH3:13])[N:12]=1.[CH3:37][O:38][C:39](=[O:47])[CH2:40][C:41]([CH3:46])([CH3:45])[CH2:42][CH:43]=O.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C.ClCCl>[CH3:37][O:38][C:39](=[O:47])[CH2:40][C:41]([CH3:46])([CH3:45])[CH2:42][CH2:43][N:18]1[C:19]2[C:20](=[CH:21][C:22]3[CH2:23][O:24][CH2:25][C:26]=3[CH:27]=2)[C@@H:14]([N:7]([CH2:6][C:5]2[CH:28]=[C:29]([C:31]([F:32])([F:33])[F:34])[CH:30]=[C:3]([C:2]([F:1])([F:35])[F:36])[CH:4]=2)[C:8]2[N:9]=[N:10][N:11]([CH3:13])[N:12]=2)[CH2:15][CH2:16][CH2:17]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 3018723Methyl 3,3-dimethyl-5-oxovalerateHCID 5049666Sodium triacetoxyborohydrideHCID 59432492(S)-(3,5-bis-trifluoromethyl-benzyl)-(3,5,6,7,8,9-hexahydro-1H-2-oxa-5-aza-cyclohepta[f]inden-9-yl)-(2-methyl-2H-tetrazol-5-yl)-amine

Product 1

HCID 59432400(S)-5-(9-[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-1,3,6,7,8,9-hexahydro-2-oxa-5-aza-cyclohepta[f]inden-5-yl)-3,3-dimethyl-pentanoic acid methyl ester

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 63651,1-DichloroethaneSolvent

Procedure

To a solution of (S)-(3,5-bis-trifluoromethyl-benzyl)-(3,5,6,7,8,9-hexahydro-1H-2-oxa-5-aza-cyclohepta[f]inden-9-yl)-(2-methyl-2H-tetrazol-5-yl)-amine (0.195 mmol) in dichloroethane (5 mL), add 3,3-dimethyl-5-oxo-pentanoic acid methyl ester (0.585 mmol) along with a catalytic amount of acetic acid. To this stirred solution add sodium triacetoxyborohydride (0.975 mmol). After stirring for 12 h, quench the reaction with aqueous sodium carbonate (5 mL) and dilute with dichloromethane (5 mL). Dry the organic portion, filter, and remove the solvent under vacuum. Chromatograph the product over silica gel, eluting with ethyl acetate/hexane (2-35%) to afford the title compound as a colorless oil. MS (ES+): 655.2 (M+H).

Workup

  1. customquench
  2. customthe reaction with aqueous sodium carbonate (5 mL)
  3. customDry the organic portion
  4. filtrationfilter
  5. customremove the solvent under vacuum
  6. washChromatograph the product over silica gel, eluting with ethyl acetate/hexane (2-35%)

Sources & evidence

ORD record
ord-25c356207a4a4ff9b4c45ac01034a2c3
Source dataset
uspto-grants-2010_08
Patent number
US07786108B2

Reaction notes

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