Sodium borohydride → HCID 52938551, compound

HRID 1807605Notes

Reaction equation

HRID 1807605 reaction equation
[C:1]([C:3]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:4]=1[CH2:5][CH2:6][C:7]2=[N:12][S@@:13]([C:15]([CH3:18])([CH3:17])[CH3:16])=[O:14])#[N:2].[BH4-].[Na+]>C1COCC1>[C:1]([C:3]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:4]=1[CH2:5][CH2:6][C@H:7]2[NH:12][S@@:13]([C:15]([CH3:18])([CH3:17])[CH3:16])=[O:14])#[N:2]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 67195576HCID 67195576, compound

Product 1

HCID 52938551HCID 52938551, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a flask containing the crude suspension of (R)-N-(4-cyano-2,3-dihydro-1H-indene-1-ylidene)-2-methylpropane-2-sulfinamide INT-48 under N2 was added THF (1.0 L) and the reaction mixture cooled to −78° C. Sodium borohydride (40.9 g, 1.08 mol) was added portion-wise over 30 mins. (The internal temperature did not rise during the addition). The reaction mixture was stirred at −78° C. for 30 mins, half out of the bath for 30 mins, then warmed to 0° C. over 1 h. The 0° C. reaction mixture was placed in an ice bath and quenched with brine (100 mL) followed by saturated sodium potassium tartrate (420 mL) and the Ti salts precipitated. The reaction mixture was diluted with EA (1.5 L) and stirred at room temperature overnight. The organic layers were decanted and washed successively with saturated NH4Cl, water, and brine. The organic layers were dried over MgSO4 and filtered through a pad of MgSO4. The filtrate was concentrated to produce 52.9 g of crude (R)-N-((R)-4-cyano-2,3-dihydro-1H-inden-1-yl)-2-methylpropane-2-sulfinamide INT-49 as a brown oil, which was used directly in the next step. LCMS-ESI (m/z) calculated for C14H18N2OS: 262.3; found 263.1 [M+H]+, tR=2.99 min. 1H NMR (400 MHz, CDCl3) δ 7.89 (d, J=7.7, 1H), 7.56 (t, J=6.8, 1H), 7.36 (t, J=7.7, 1H), 4.97 (q, J=7.5, 1H), 3.50 (d, J=7.6, 1H), 3.22 (ddd, J=16.9, 8.8, 3.9, 1H), 3.01 (dt, J=22.4, 6.9, 1H), 2.70-2.53 (m, 1H), 2.15-1.95 (m, 1H), 1.33-1.20 (m, 9H).

Workup

  1. additionTo a flask containing the crude
  2. addition(The internal temperature did not rise during the addition)
  3. waithalf out of the bath for 30 mins
  4. temperaturewarmed to 0° C. over 1 h
  5. customThe 0° C. reaction mixture
  6. customwas placed in an ice bath
  7. customquenched with brine (100 mL)
  8. customthe Ti salts precipitated
  9. additionThe reaction mixture was diluted with EA (1.5 L)
  10. stirringstirred at room temperature overnight
  11. customThe organic layers were decanted
  12. washwashed successively with saturated NH4Cl, water, and brine
  13. dry with materialThe organic layers were dried over MgSO4
  14. filtrationfiltered through a pad of MgSO4
  15. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-2f52bcfa9c444a1b909fad1b46051571
Source dataset
uspto-grants-2013_01
Patent number
US08357706B2

Reaction notes

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