Acetic Acid → HCID 11949606, compound

HRID 1009979Notes

Reaction equation

HRID 1009979 reaction equation
C(OC([O:8][NH:9][C:10]([C:12]1[S:16][C:15]2[CH:17]=[C:18]([CH:21]=O)[CH:19]=[CH:20][C:14]=2[CH:13]=1)=[O:11])C)C(C)C.[CH:23]1([O:28][C:29](=[O:50])[C@@H:30]([NH:42]C(OC(C)(C)C)=O)[CH2:31][CH2:32][O:33][C:34]2[CH:39]=[CH:38][C:37]([CH2:40][NH2:41])=[CH:36][CH:35]=2)[CH2:27][CH2:26][CH2:25][CH2:24]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>ClCCCl.C(O)(C(F)(F)F)=O.C(Cl)Cl>[CH:23]1([O:28][C:29](=[O:50])[C@@H:30]([NH2:42])[CH2:31][CH2:32][O:33][C:34]2[CH:35]=[CH:36][C:37]([CH2:40][NH:41][CH2:21][C:18]3[CH:19]=[CH:20][C:14]4[CH:13]=[C:12]([C:10](=[O:11])[NH:9][OH:8])[S:16][C:15]=4[CH:17]=3)=[CH:38][CH:39]=2)[CH2:27][CH2:26][CH2:25][CH2:24]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 57971713HCID 57971713, compoundHCID 57994336HCID 57994336, compound

Product 1

HCID 11949606HCID 11949606, compoundYield 15.1%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Procedure

To a stirred solution of 6-formyl-benzo[b]thiophene-2-carboxylic acid (1-isobutoxy-ethoxy) amide (Scheme 13) (0.128 g, 0.40 mmol) in DCE (5 ml) was added (S)-4-(4-aminomethyl-phenoxy)-2-tert-butoxycarbonylamino-butyric acid cyclopentyl ester (0.156 g, 0.40 mmol) followed by sodium triacetoxyborohydride (0.253 g, 1.1 g mmol) and glacial acetic acid (0.023 ml, 0.40 mmol). After stirring for 18 hours the mixture was quenched using saturated aqueous NaHCO3 solution (5 ml). The organic layer was separated, washed further with saturated aqueous NaHCO3 solution (2×5 ml), dried (MgSO4) and the solvent removed in vacuo to give a yellow residue. The residue was redissolved in a TFA/DCM solution (1:1, 5 ml). After stirring the solution for 45 minutes the solvent was removed in vacuo. Purification by preparative HPLC gave the product as a white solid (0.030 g, 15% yield). LCMS purity 96.1%, m/z 498 [M++H]+, 1H NMR (300 MHz, DMSO), δ: 1.50-1.90 (9H, m, CH2×4, CH), 2.25 (2H, m, CH2), 4.10-4.40 (7H, m, CH2×3, CH), 5.20 (1H, m, CH), 6.95 (2H, d, ArH×2, J=8.6 Hz), 7.45 (2H, d, ArH×2, J=8.6 Hz), 7.55 (1H, d, ArH, J=7.8 Hz), 8.00 (2H, m, ArH×2), 8.15 (1H, s, ArH), 8.40 (2H, br s, ArH×2), 9.20 (2H, m ArH×2).

Workup

  1. customwas quenched
  2. customThe organic layer was separated
  3. washwashed further with saturated aqueous NaHCO3 solution (2×5 ml)
  4. dry with materialdried (MgSO4)
  5. customthe solvent removed in vacuo
  6. customto give a yellow residue
  7. stirringAfter stirring the solution for 45 minutes the solvent
  8. customwas removed in vacuo
  9. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-fb49772055494e529ab4e749bf0466aa
Source dataset
uspto-grants-2011_07
Patent number
US07973181B2

Reaction notes

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