Sodium triacetoxyborohydride → HCID 24877154, compound

HRID 887957Notes

Reaction equation

HRID 887957 reaction equation
[NH2:1][C@@H:2]([CH2:28][CH:29]([CH3:31])[CH3:30])[C:3]([N:5]1[CH2:10][CH2:9][CH2:8][CH:7]([N:11]([CH:25]2[CH2:27][CH2:26]2)[S:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=2)(=[O:14])=[O:13])[CH2:6]1)=[O:4].[BH-](O[C:42]([CH3:44])=[O:43])(OC(C)=O)OC(C)=O.[Na+].CCO[C:49]([CH3:51])=O.[CH3:52]O>ClCCCl>[CH:25]1([N:11]([CH:7]2[CH2:8][CH2:9][CH2:10][N:5]([C:3](=[O:4])[C@@H:2]([NH:1][CH2:52][CH:49]([C:42]([CH3:44])=[O:43])[CH3:51])[CH2:28][CH:29]([CH3:31])[CH3:30])[CH2:6]2)[S:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:23])([F:24])[F:22])[CH:16]=2)(=[O:14])=[O:13])[CH2:26][CH2:27]1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 21584119Ethylacetate methanolHCID 24877035HCID 24877035, compound

Product 1

HCID 24877154HCID 24877154, compoundYield 32%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

(2S)N-Cyclopropyl-N-[1-(2-methylcarbonylpropylamino-4-methylpentanoyl)piperidin-3-yl]-3-trifluoromethylbenzenesulfonamide (20) was prepared as follows. A solution of compound 8 prepared in Example 2 (100 mg, 0.22 mmol), compound 19 (12 mg, 0.22 mmol, Aldrich) and 4 Å molecular sieves (500 mg) in 2 mL of 1,2-dichloroethane (DCE) was shaken at room temperature for 10 minutes, and then NaB(OAc)3H (43 mg, 0.22 mmol) was charged. The resulting mixture was shaken at room temperature for 24 hours. The reaction mixture was quenched with MeOH (0.2 mL), water (2 mL) was added and the mixture was extracted with DCM (3×4 mL). The organic layers were combined and washed with brine, dried over Na2SO3, concentrated under vacuum and purified by column (silica gel, EtOAc, then EtOAc/MeOH 10/1) to give the title compound 20 as white solid (40 mg, yield 32%). 1H NMR (400 MHz, CD3OD): δ 8.01-8.26 (m, 3H), 7.86-7.93 (m, 1H), 5.0-5.15 (m, 0.4H), 4.45-4.55 (m, 1.2H), 3.75-4.35 (m, 1.3H), 2.55-3.45 (m, 5H), 0.75-2.20 (m, 26H); LC: 98%; MS: m/z=568 (M+Na+).

Workup

  1. custom(2S)N-Cyclopropyl-N-[1-(2-methylcarbonylpropylamino-4-methylpentanoyl)piperidin-3-yl]-3-trifluoromethylbenzenesulfonamide (20) was prepared
  2. customThe reaction mixture was quenched with MeOH (0.2 mL), water (2 mL)
  3. additionwas added
  4. extractionthe mixture was extracted with DCM (3×4 mL)
  5. washwashed with brine
  6. dry with materialdried over Na2SO3
  7. concentrationconcentrated under vacuum
  8. custompurified by column (silica gel, EtOAc

Sources & evidence

ORD record
ord-df31d55037b64b7b868aa63c58fb7f14
Source dataset
uspto-grants-2012_08
Patent number
US08247442B2

Reaction notes

Loading…