Isopropyl chloroformate → HCID 86650177, compound

HRID 448588Notes

Reaction equation

HRID 448588 reaction equation
[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[N:19]=[CH:18][N:17]=[C:16]([N:20]3[C:28]4[C:23](=[CH:24][C:25]([C:29](O)=[O:30])=[CH:26][CH:27]=4)[CH2:22][CH2:21]3)[CH:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2].C(N(CC)CC)C.ClC(OC(C)C)=O.[BH4-].[Na+]>C1COCC1.O>[CH:1]([O:4][C:5]([N:7]1[CH2:8][CH2:9][CH:10]([O:13][C:14]2[CH:15]=[C:16]([N:20]3[C:28]4[C:23](=[CH:24][C:25]([CH2:29][OH:30])=[CH:26][CH:27]=4)[CH2:22][CH2:21]3)[N:17]=[CH:18][N:19]=2)[CH2:11][CH2:12]1)=[O:6])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 7917Isopropyl chloroformateHCID 8471TriethylamineHCID 4311764Sodium borohydrideHCID 58116602HCID 58116602, compound

Product 1

HCID 86650177HCID 86650177, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

19c was dissolved in 1 mL of THF with 0.5 mL of triethylamine (3.59 mmol). Isopropyl chloroformate (1M in toluene, 2.25 mL, 2.25 mmol) was added and the mixture was stirred at room temperature for 2 h. Water (1 mL) was added followed by NaBH4 (0.5 g, 13.2 mmol) and the mixture was sonicated for 2 minutes and stirred at room temperature for 1 h. THF was removed under vacuum and the aqueous mixture was acidified with 1N HCl, extracted with DCM (3×10 mL) and the combined extracts were washed with brine (10 mL). The solution was dried, filtered and evaporated. The residue was purified by preparative HPLC to afford 19-1 (tR=3.0, Method 5) as well as a small amount of 4-[6-(5-hydroxymethyl-2,3-dihydro-indol-1-yl)-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester 19-2. tR=5.21 (Method 5).

Workup

  1. customthe mixture was sonicated for 2 minutes
  2. stirringstirred at room temperature for 1 h
  3. customTHF was removed under vacuum
  4. extractionextracted with DCM (3×10 mL)
  5. washthe combined extracts were washed with brine (10 mL)
  6. customThe solution was dried
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-9091df4514a544ca93fa60bf007ff1fe
Source dataset
uspto-grants-2013_07
Patent number
US08481731B2

Reaction notes

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