Sodium triacetoxyborohydride → N-[2-({(3R)-1-[4-Hydroxy-4-(4-iodophenyl)cyclohexyl]pyrrolidin-3-yl}amino)-2 oxoethyl]-3-(trifluoromethyl)benzamide

HRID 1025774Notes

Reaction equation

HRID 1025774 reaction equation
[OH:1][C:2]1([C:9]2[CH:14]=[CH:13][C:12]([I:15])=[CH:11][CH:10]=2)[CH2:7][CH2:6][C:5](=O)[CH2:4][CH2:3]1.[NH:16]1[CH2:20][CH2:19][C@@H:18]([NH:21][C:22]([CH2:24][NH:25][C:26](=[O:37])[C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([C:33]([F:36])([F:35])[F:34])[CH:28]=2)=[O:23])[CH2:17]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl>[OH:1][C:2]1([C:9]2[CH:14]=[CH:13][C:12]([I:15])=[CH:11][CH:10]=2)[CH2:7][CH2:6][CH:5]([N:16]2[CH2:20][CH2:19][C@@H:18]([NH:21][C:22](=[O:23])[CH2:24][NH:25][C:26](=[O:37])[C:27]3[CH:32]=[CH:31][CH:30]=[C:29]([C:33]([F:34])([F:36])[F:35])[CH:28]=3)[CH2:17]2)[CH2:4][CH2:3]1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 59556069(R)-N-(2-oxo-2-(pyrrolidin-3-ylamino)ethyl)-3-(trifluoromethyl)benzamideHCID 595561854-Hydroxy-4-(4-iodophenyl)cyclohexanone

Product 1

HCID 66787502N-[2-({(3R)-1-[4-Hydroxy-4-(4-iodophenyl)cyclohexyl]pyrrolidin-3-yl}amino)-2 oxoethyl]-3-(trifluoromethyl)benzamideYield 36.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-hydroxy-4-(4-iodophenyl)cyclohexanone (624 mg, 2 mmol) in CH2Cl2 (10 mL) was added N-((3R)-pyrrolidin-3-ylcarbamoylmethyl)-3-trifluoromethylbenzamide (730 mg, 2 mmol) and then NaBH(OAc)3 (666 mg, 3 mmol). After stirred for 1 h, the reaction was quenched with 10% NaHCO3, and extracted with EtOAc. The organic extracts were combined, washed with saline solution, dried over sodium sulfate, concentrated in vacuo. The residue was chromatographed on silica gel, eluting with 1% NH4OH in ethyl acetate/methanol (100/0 to 10/90) to yield the major isomer (544 mg, 44.2%) and the minor isomer (446 mg, 36.3% yield). For the major isomer, LCMS: 615.2 (M+H+, 100%); 1H NMR: (CDCl3) δ 8.09, (s, 1H); 7.98, (d, 1H); 7.77, (d, 1H); 7.67, (d, 2H); 7.57, (t, 1H); 7.28, (d, 2H); 7.22, (t, 1H, NH); 6.44, (d, 1H, NH); 4.49, (m, 1H); 4.12, (m, 2H); 2.87, (m, 1H); 2.64, (m, 2H); 2.38, (m, 1H); 2.25, (m, 4H); 1.93, (m, 2H); 1.54-1.70, (m, 6H).

Workup

  1. customthe reaction was quenched with 10% NaHCO3
  2. extractionextracted with EtOAc
  3. washwashed with saline solution
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was chromatographed on silica gel
  7. washeluting with 1% NH4OH in ethyl acetate/methanol (100/0 to 10/90)
  8. customto yield the major isomer (544 mg, 44.2%)

Sources & evidence

ORD record
ord-67b6c2338bb34edb8ba406da6f94f2f9
Source dataset
uspto-grants-2014_05
Patent number
US08729063B2

Reaction notes

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