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-ylmethyl}-thiophene-2-carboxylic acid

HRID 507119Notes

Reaction equation

HRID 507119 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.[CH:37]([C:39]1[S:43][C:42]([C:44]([OH:46])=[O:45])=[CH:41][CH:40]=1)=O.C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClC(Cl)C.ClCCl>[F:36][C:2]([F:1])([F:35])[C:3]1[CH:4]=[C:5]([CH:28]=[C:29]([C:31]([F:32])([F:33])[F:34])[CH:30]=1)[CH2:6][N:7]([C:8]1[N:9]=[N:10][N:11]([CH3:13])[N:12]=1)[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[N:18]([CH2:37][C:39]2[S:43][C:42]([C:44]([OH:46])=[O:45])=[CH:41][CH:40]=2)[CH2:17][CH2:16][CH2:15]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 8188825-Formyl-2-thiophenecarboxylic AcidHCID 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 11614406(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-ylmethyl}-thiophene-2-carboxylic acid

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 (Example 73, Step 7) (0.16 mmol) in dichloroethane (5 mL), add 5-formyl-thiophene-2-carboxylic acid (0.63 mmol) followed by acetic acid (cat.). Add NaB(OAc)3H (0.78 mmol) and stir the mixture at room temperature for 14 h. Dilute the reaction with dichloromethane (10 mL) and quench with water (5 mL). Separate the organics and wash the aqueous with dichloromethane (2×10 mL). Dry the combined organics over Na2SO4, filter, and remove the solvent under vacuum. Chromatograph the product over silica gel eluting with MeOH/DCM (1-5%) to provide the title compound as a colorless foam. MS (ES+): 651 (M−H).

Workup

  1. additionDilute
  2. customquench with water (5 mL)
  3. customSeparate the organics and
  4. washwash the aqueous with dichloromethane (2×10 mL)
  5. dry with materialDry the combined organics over Na2SO4
  6. filtrationfilter
  7. customremove the solvent under vacuum

Sources & evidence

ORD record
ord-94f3d10ec33a44a99e8210f07a761a98
Source dataset
uspto-grants-2010_08
Patent number
US07786108B2

Reaction notes

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